Trial Outcomes & Findings for Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU (NCT NCT00520975)
NCT ID: NCT00520975
Last Updated: 2025-03-28
Results Overview
Progression-free survival (PFS) was defined as time from date of randomization to first disease progression, new second breast primaries, or to death from any cause, whichever occurred first, otherwise cases were censored at date last documented to be free of progression. Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the median PFS.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
96 participants
Primary outcome timeframe
assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years
Results posted on
2025-03-28
Participant Flow
Ninety-six patients were randomized between November 9, 2007 and October 28, 2009 when the trial closed due to slow accrual.
Participant milestones
| Measure |
Arm A (Chemotherapy and Placebo)
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
Arm B (Chemotherapy and Bevacizumab)
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Overall Study
STARTED
|
48
|
48
|
|
Overall Study
Treated and Reported Adverse Events Data
|
47
|
45
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
48
|
48
|
Reasons for withdrawal
| Measure |
Arm A (Chemotherapy and Placebo)
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
Arm B (Chemotherapy and Bevacizumab)
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Overall Study
Disease progression
|
31
|
23
|
|
Overall Study
Adverse Event
|
7
|
10
|
|
Overall Study
Death
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
3
|
5
|
|
Overall Study
Other therapy
|
2
|
4
|
|
Overall Study
Other reasons
|
4
|
2
|
|
Overall Study
Not start protocol therapy
|
1
|
2
|
Baseline Characteristics
Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU
Baseline characteristics by cohort
| Measure |
Arm A (Chemotherapy and Placebo)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
Arm B (Chemotherapy and Bevacizumab)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Total
n=96 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 Years
n=99 Participants
|
55 Years
n=107 Participants
|
55 Years
n=206 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=99 Participants
|
48 Participants
n=107 Participants
|
96 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 yearsPopulation: All randomized patients
Progression-free survival (PFS) was defined as time from date of randomization to first disease progression, new second breast primaries, or to death from any cause, whichever occurred first, otherwise cases were censored at date last documented to be free of progression. Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the median PFS.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Progression-free Survival
|
13.8 Months
Interval 10.6 to 22.5
|
11.1 Months
Interval 8.7 to 12.4
|
SECONDARY outcome
Timeframe: assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 yearsPopulation: All randomized patients
Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. Kaplan-Meier method was used to estimate the median OS.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Overall Survival
|
63.0 Months
Interval 34.4 to 72.8
|
49.1 Months
Interval 37.2 to 67.4
|
SECONDARY outcome
Timeframe: assessed at baseline, at 3 and 6 months after study entryPopulation: All randomized patients
Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Proportion of progression-free at 6 months was calculated using the Kaplan-Meier method.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Proportion of Progression-free at 6 Months
|
0.871 proportion of participants
Interval 0.735 to 0.939
|
0.826 proportion of participants
Interval 0.682 to 0.908
|
SECONDARY outcome
Timeframe: assessed at baseline, every 12 weeks while on treatment, then very 3 months if patient is <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years from study entry until disease progressionPopulation: All randomized patients
Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s).
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=48 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Overall Response Rate
|
0.604 proportion of participants
Interval 0.453 to 0.742
|
0.542 proportion of participants
Interval 0.392 to 0.686
|
SECONDARY outcome
Timeframe: assessed every 3 months while on treatment and at 3 months post treatmentPopulation: All patients who began protocol treatment
Clinical congestive heart failure (CHF) was assessed using Left Ventricular Ejection Fraction (LVEF) and symptom information via the Cardiac Toxicity Form as well as symptom information collected via the Adverse Event Form. Clinical CHF was defined as symptomatic decline in LVEF to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=45 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=47 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Number of Patients Experiencing Congestive Heart Failure
|
4 participants
|
1 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapyPopulation: All patients who reported their fatigue level using FACIT Fatigue subscale at both baseline and cycle 6 induction
Fatigue level was measured using Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue subscale. Participants indicated their level of fatigue across 13 items, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient was calculated by taking the reverse of each item (unless specified not to), taking the sum of those items, multiplying the sum by the number of items in the scale, and then dividing that number by the number of answered items. Total score ranged from 0 to 52 with higher scores representing less fatigue.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=30 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=26 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Change in Fatigue Level Between Baseline and Cycle 6 Induction
|
3.0 scores on a scale
Interval -2.0 to 16.0
|
2.0 scores on a scale
Interval -5.0 to 13.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapyPopulation: All patients who reported their fatigue level using FACIT Fatigue subscale at both baseline and cycle 6 induction
Participants indicated their level of breast symptoms across 8 items using the Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network (FACT/NCCN) FBSI scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 32 with higher scores representing fewer symptoms.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=30 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=27 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Change in FACT/NCCN Breast Symptom Index (FBSI) Between Baseline and Cycle 6 Induction
|
2 scores on a scale
Interval -26.0 to 18.0
|
1 scores on a scale
Interval -14.0 to 9.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapyPopulation: All patients who reported their neurotoxicity level using FACT/GOG-Ntx scale at both baseline and cycle 6 induction
Participants indicated their level of neurotoxicity symptoms across 4 items using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient ranged from 0 to 16 with higher scores representing fewer neurotoxic symptoms.
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=30 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=26 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Change in Neurotoxicity Level Between Baseline and Cycle 6 Induction
|
3 scores on a scale
Interval -2.0 to 16.0
|
2 scores on a scale
Interval -5.0 to 13.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapyPopulation: All patients who reported their level of experiencing side effects using FACT item G5 at both baseline and cycle 6 induction
Participants indicated their level of experiencing side effects across 1 item (Functional Assessment of Cancer Therapy \[FACT\] item G5) on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 4 with a higher score representing better quality of life (QOL).
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=29 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=25 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Change in Level of Experiencing Side Effects Between Baseline and Cycle 6 Induction
|
1 scores on a scale
Interval -2.0 to 3.0
|
0 scores on a scale
Interval -2.0 to 2.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baseline prior to starting protocol therapyPopulation: Patients who had blood sample drawn at baseline prior to starting protocol therapy
Number of circulating tumor cells per 7.5mL blood were counted prior to starting protocol therapy
Outcome measures
| Measure |
Arm B (Chemotherapy and Bevacizumab)
n=34 Participants
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
Arm A (Chemotherapy and Placebo)
n=31 Participants
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Number of Circulating Tumor Cells at Baseline
|
2 number of cells per 7.5 mL blood
Interval 0.0 to 690.0
|
4 number of cells per 7.5 mL blood
Interval 0.0 to 126.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: assessed at baselineTissue sections from the primary or metastatic paraffin blocks were subjected to VEGF immunohistochemistry (IHC). The VEGF cytoplasmic staining intensity was evaluated semiquantitavely using a classification from 0 to 3, with 0 representing lack of staining, 1 = low staining intensity, 2 = intermediate staining intensity and 3 = strong staining intensity. The fraction of positively staining cells will be determined as well (0 = lack of staining, 1 ≤ 1% cell staining, 2 = 1 - 10% cell staining, 3 = 10 - 50% cell staining, 4 = 50 - 90% cells staining and 5 ≤ 90% cells staining) (48). Staining intensity score zero and fraction of positively staining cells of ≤ 1% (scores zero and 1) will be considered as absence of staining and therefore negative overexpression of VEGF.
Outcome measures
Outcome data not reported
Adverse Events
Arm A (Chemotherapy and Placebo)
Serious events: 26 serious events
Other events: 19 other events
Deaths: 0 deaths
Arm B (Chemotherapy and Bevacizumab)
Serious events: 34 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Arm A (Chemotherapy and Placebo)
n=47 participants at risk
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
Arm B (Chemotherapy and Bevacizumab)
n=45 participants at risk
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Immune system disorders
Allergic reaction
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
8.9%
4/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Blood and lymphatic system disorders
Anemia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Leukocytes decreased
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Lymphopenia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Neutrophils decreased
|
17.0%
8/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
20.0%
9/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Platelets decreased
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Cardiac troponin T (cTnT) increased
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Vascular disorders
Hypertension
|
10.6%
5/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
13.3%
6/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
8.9%
4/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Cardiac disorders
Cardiomyopathy, restrictive
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Fatigue
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
11.1%
5/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Fever w/o neutropenia
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Weight loss
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Skin and subcutaneous tissue disorders
Ulceration
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Injury, poisoning and procedural complications
Wound - non-infectious
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Anorexia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.3%
2/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
8.5%
4/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Nausea
|
4.3%
2/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Vomiting
|
4.3%
2/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Renal and urinary disorders
Urinary hemorrhage NOS
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Infections and infestations
Infection w/ gr3-4 neut, bronchus
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Infections and infestations
Infection w/ gr3-4 neut, heart
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Infections and infestations
Infection Gr0-2 neut, catheter
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Infections and infestations
Infection Gr0-2 neut, skin
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Infections and infestations
Infection Gr0-2 neut, blood
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Aspartate aminotransferase increased
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Blood bilirubin increased
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Creatinine increased
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Renal and urinary disorders
Proteinuria
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
8.9%
4/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Extremity-lower (gait/walking)
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Musculoskeletal and connective tissue disorders
Nonneuropathic generalized weakness
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Psychiatric disorders
Confusion
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Psychiatric disorders
Depression
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Nervous system disorders
Neuropathy-motor
|
4.3%
2/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Nervous system disorders
Neuropathy-sensory
|
6.4%
3/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
11.1%
5/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Nervous system disorders
Neurologic-other
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Chest/thoracic pain NOS
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Nervous system disorders
Head/headache
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Musculoskeletal and connective tissue disorders
Joint, pain
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Pain-other
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Renal and urinary disorders
Renal failure
|
4.3%
2/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Reproductive system and breast disorders
Irregular menses
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
Other adverse events
| Measure |
Arm A (Chemotherapy and Placebo)
n=47 participants at risk
INDUCTION THERAPY: Patients receive trastuzumab IV over 30-90 minutes on days 1, 8, 15, and 22 and paclitaxel IV over 60 minutes with or without carboplatin IV over 60 minutes on days 1, 8, and 15. Patients also receive placebo IV over 30-90 minutes on day 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Carboplatin: Given IV
Paclitaxel: Given IV
Placebo: Given IV
Trastuzumab: Given IV
|
Arm B (Chemotherapy and Bevacizumab)
n=45 participants at risk
INDUCTION THERAPY: Patients receive trastuzumab and paclitaxel with or without carboplatin as in Arm A. Patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 4 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Beginning 1 week after the last dose of induction trastuzumab, patients receive trastuzumab IV over 30-90 minutes and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Bevacizumab: Given IV
Carboplatin: Given IV
Paclitaxel: Given IV
Trastuzumab: Given IV
|
|---|---|---|
|
Immune system disorders
Allergic reaction
|
6.4%
3/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Blood and lymphatic system disorders
Anemia
|
8.5%
4/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
4.4%
2/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Investigations
Leukocytes decreased
|
6.4%
3/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
2.1%
1/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
13.3%
6/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
General disorders
Fatigue
|
14.9%
7/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
8.5%
4/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
2.2%
1/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Metabolism and nutrition disorders
Anorexia
|
6.4%
3/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Diarrhea w/o prior colostomy
|
8.5%
4/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
20.0%
9/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Gastrointestinal disorders
Nausea
|
8.5%
4/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
0.00%
0/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Respiratory, thoracic and mediastinal disorders
Nose, hemorrhage
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
6.7%
3/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
11.1%
5/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Nervous system disorders
Neuropathy-sensory
|
14.9%
7/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
22.2%
10/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/47 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
8.9%
4/45 • Assessed every cycle (1 cycle=4 weeks during Induction therapy, 1 cycle=3 weeks during Maintenance therapy) while on treatment and for 30 days after the end of treatment
After discontinuation of treatment, severe (Grade ≥ 3) long term toxicity that had not been previously reported were collected via the Long term follow-up form using the following schedule: every 3 months within 2 years of registration, then every 6 months in years 2-5, annually afterward until year 10.
|
Additional Information
ECOG-ACRIN statistician
ECOG-ACRIN Statistical Office
Phone: 617-632-3012
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60