Trial Outcomes & Findings for Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer (NCT NCT00887575)
NCT ID: NCT00887575
Last Updated: 2016-09-07
Results Overview
Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
54 participants
Primary outcome timeframe
at weeks 26-30
Results posted on
2016-09-07
Participant Flow
Patients were recruited at multiple dose levels into the Dose Escalation (Phase I) portion of this study to determine the safest dose of this regimen (MTD- Maximum Tolerated Dose). Upon determination of this dose, patients being treated at the MTD proceeded to the Dose Expansion (Phase II) portion of the study and additional patients were recruited
Participant milestones
| Measure |
Dose Level I
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Maintenance - Sunitinib PO (25mg) daily
|
Dose Level II
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
|
Dose Level III
Paclitaxel IV (80 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 6) day 1 of every cycle and Sunitinib PO (25mg) daily.
|
|---|---|---|---|
|
Phase I
STARTED
|
6
|
6
|
3
|
|
Phase I
COMPLETED
|
6
|
0
|
0
|
|
Phase I
NOT COMPLETED
|
0
|
6
|
3
|
|
Phase II - Neoadjuvant Therapy
STARTED
|
41
|
0
|
0
|
|
Phase II - Neoadjuvant Therapy
COMPLETED
|
16
|
0
|
0
|
|
Phase II - Neoadjuvant Therapy
NOT COMPLETED
|
25
|
0
|
0
|
|
Phase II - Maintenance Therapy
STARTED
|
8
|
0
|
0
|
|
Phase II - Maintenance Therapy
COMPLETED
|
6
|
0
|
0
|
|
Phase II - Maintenance Therapy
NOT COMPLETED
|
2
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Neoadjuvant Sunitinib With Paclitaxel/Carboplatin in Patients With Triple-Negative Breast Cancer
Baseline characteristics by cohort
| Measure |
All Patients
n=50 Participants
Includes all patients treated at all dose levels
|
|---|---|
|
Age, Continuous
|
53 Years
n=99 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
50 participants
n=99 Participants
|
|
Baseline ECOG Performance Status
ECOG Performance Status = 0
|
45 participants
n=99 Participants
|
|
Baseline ECOG Performance Status
ECOG Performance Status = 1
|
5 participants
n=99 Participants
|
|
Menopausal Status
Postmenopausal
|
34 Participants
n=99 Participants
|
|
Menopausal Status
Premenopausal
|
16 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: at weeks 26-30Population: Patients treated at Dose Level I (Phase I and Phase II) who underwent surgery
Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples.
Outcome measures
| Measure |
Phase II- Sunitinib/Paclitaxel/Carboplatin
n=32 Participants
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
|
|---|---|
|
Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin
|
12 participants
|
SECONDARY outcome
Timeframe: Days 1, 8, and 15 of each 4-week cycle up to 24 weeks during neoadjuvant treatment, and every 4 weeks during maintenance treatmentPopulation: The safety analysis includes all eligible patients enrolled at the MTD, whether or not treatment was recieved (6 patients in Phase I were treated at the MTD, 39 patients were enrolled in Phase II, 3 were deemed ineligible after enrollment-thus 42 patients are included in the safety analysis, including 1 eligible patient who was not treated)
Assessments will be made through analysis of reported incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) at the phase II dose
Outcome measures
| Measure |
Phase II- Sunitinib/Paclitaxel/Carboplatin
n=42 Participants
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
|
|---|---|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Neutropenia
|
34 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Anemia
|
30 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Thrombocytopenia
|
30 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Leukopenia
|
30 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Febrile neutropenia
|
3 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Fatigue
|
32 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Alopecia
|
26 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Nausea/Vomiting
|
24 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Constipation
|
22 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Diarrhea
|
21 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Mucositis
|
17 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Dysgeusia
|
17 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Peripheral neuropathy
|
17 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Dyspepsia
|
13 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Dyspnea
|
12 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Anorexia
|
10 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Fever
|
9 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Bleeding
|
9 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Insomnia
|
9 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Pain in extremity
|
9 participants
|
|
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Skin toxicity
|
9 participants
|
SECONDARY outcome
Timeframe: Days 1, 8 and 15 of each cycle, minimum of 12 weeksPopulation: Patients who were enrolled, treated at the MTD and completed at least 3 cycles of neoadjuvant therapy
Assessed by clinical, radiologic and surgical determinations before and after neoadjuvant therapy. Measurable lesions will be defined by RECIST criteria v1.1.
Outcome measures
| Measure |
Phase II- Sunitinib/Paclitaxel/Carboplatin
n=29 Participants
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
|
|---|---|
|
Overall Response Rate (ORR)
|
25 participants
|
SECONDARY outcome
Timeframe: every 4 weeks from date of surgery until treatment discontinuation or death, expected average 18 monthsDefined as the time between day of surgery to first documented disease occurrence or death due to any cause.
Outcome measures
| Measure |
Phase II- Sunitinib/Paclitaxel/Carboplatin
n=41 Participants
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
|
|---|---|
|
Disease-free Survival
Median Disease-Free Survival
|
15.8357 months
Interval 6.8665 to
Not enough data available for this outcome measure
|
|
Disease-free Survival
Median Overall Survival
|
NA months
Interval 40.9692 to
Not enough data available for this outcome measure
|
SECONDARY outcome
Timeframe: 24 monthsDefined as the time between Day 1 Cycle 1 to time of death from any cause.
Outcome measures
| Measure |
Phase II- Sunitinib/Paclitaxel/Carboplatin
n=41 Participants
Systemic Therapy based on maximum tolerated dose (MTD) of the Phase I portion
|
|---|---|
|
Overall Survival (OS)
|
0.8912 probability of overall survival at 24 m
Interval 0.734 to 0.958
|
Adverse Events
Dose Level I
Serious events: 3 serious events
Other events: 41 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level I
n=41 participants at risk
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Maintenance - Sunitinib PO (25mg) daily
|
|---|---|
|
Renal and urinary disorders
ACUTE RENAL FAILURE
|
2.4%
1/41 • Number of events 1
|
|
Investigations
ALKALINE PHOSPHATASE INCREASED
|
2.4%
1/41 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
2.4%
1/41 • Number of events 1
|
|
Blood and lymphatic system disorders
ANEMIA
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
ANOREXIA
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
2.4%
1/41 • Number of events 1
|
|
Investigations
CREATININE LEVELS INCREASED
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
DIARRHEA
|
2.4%
1/41 • Number of events 2
|
|
Nervous system disorders
DIZZINESS
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
DYSPEPSIA
|
2.4%
1/41 • Number of events 1
|
|
General disorders
EDEMA
|
2.4%
1/41 • Number of events 3
|
|
General disorders
FATIGUE
|
4.9%
2/41 • Number of events 4
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
FLATULENCE
|
2.4%
1/41 • Number of events 1
|
|
Injury, poisoning and procedural complications
FRACTURE
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
HEADACHE
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPERMAGNESEMIA
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
HYPERTENSION
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPOCALCEMIA
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPOMAGNESEMIA
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
HYPONATREMIA
|
2.4%
1/41 • Number of events 1
|
|
Psychiatric disorders
INSOMNIA
|
2.4%
1/41 • Number of events 1
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
2.4%
1/41 • Number of events 3
|
|
Gastrointestinal disorders
MUCOSITIS
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
NAUSEA
|
4.9%
2/41 • Number of events 2
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
4.9%
2/41 • Number of events 5
|
|
Infections and infestations
PHARYNGITIS
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
TASTE ALTERATION
|
2.4%
1/41 • Number of events 1
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
4.9%
2/41 • Number of events 3
|
|
Gastrointestinal disorders
VOMITING
|
4.9%
2/41 • Number of events 3
|
|
Injury, poisoning and procedural complications
WOUND COMPLICATION
|
2.4%
1/41 • Number of events 1
|
Other adverse events
| Measure |
Dose Level I
n=41 participants at risk
Neoadjuvant - Paclitaxel IV (70 mg/m\^2) days 1, 8 and 15 of each cycle, Carboplatin IV (AUC = 5) day 1 of every cycle and Sunitinib PO (25mg) daily.
Maintenance - Sunitinib PO (25mg) daily
|
|---|---|
|
Investigations
ALANINE AMINOTRANSFERA
|
7.3%
3/41 • Number of events 5
|
|
Investigations
ALKALINE PHOSPHATASE INCREASED
|
7.3%
3/41 • Number of events 5
|
|
Immune system disorders
ALLERGIC REACTION
|
9.8%
4/41 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
ALLERGIC RHINITIS
|
9.8%
4/41 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
ALOPECIA
|
58.5%
24/41 • Number of events 79
|
|
Blood and lymphatic system disorders
ANEMIA
|
82.9%
34/41 • Number of events 135
|
|
Metabolism and nutrition disorders
ANOREXIA
|
26.8%
11/41 • Number of events 25
|
|
Psychiatric disorders
ANXIETY
|
9.8%
4/41 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
19.5%
8/41 • Number of events 23
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
9.8%
4/41 • Number of events 7
|
|
Musculoskeletal and connective tissue disorders
ASTHENIA
|
7.3%
3/41 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
12.2%
5/41 • Number of events 11
|
|
Eye disorders
BLURRED VISION
|
9.8%
4/41 • Number of events 16
|
|
Musculoskeletal and connective tissue disorders
BONE PAIN
|
9.8%
4/41 • Number of events 6
|
|
Reproductive system and breast disorders
BREAST PAIN
|
12.2%
5/41 • Number of events 12
|
|
General disorders
CHEST PAIN
|
9.8%
4/41 • Number of events 8
|
|
Gastrointestinal disorders
CONSTIPATION
|
48.8%
20/41 • Number of events 60
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
22.0%
9/41 • Number of events 23
|
|
Metabolism and nutrition disorders
DEHYDRATION
|
9.8%
4/41 • Number of events 5
|
|
Psychiatric disorders
DEPRESSION
|
7.3%
3/41 • Number of events 5
|
|
Gastrointestinal disorders
DIARRHEA
|
48.8%
20/41 • Number of events 54
|
|
Nervous system disorders
DIZZINESS
|
34.1%
14/41 • Number of events 30
|
|
Gastrointestinal disorders
DRY MOUTH
|
9.8%
4/41 • Number of events 14
|
|
Skin and subcutaneous tissue disorders
DRY SKIN
|
9.8%
4/41 • Number of events 6
|
|
Nervous system disorders
DYSGEUSIA
|
14.6%
6/41 • Number of events 11
|
|
Gastrointestinal disorders
DYSPEPSIA
|
24.4%
10/41 • Number of events 29
|
|
Respiratory, thoracic and mediastinal disorders
DYSPNEA
|
31.7%
13/41 • Number of events 33
|
|
General disorders
EDEMA
|
7.3%
3/41 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
EPISTAXIS
|
24.4%
10/41 • Number of events 25
|
|
Skin and subcutaneous tissue disorders
ERYTHEMA
|
9.8%
4/41 • Number of events 5
|
|
General disorders
FATIGUE
|
82.9%
34/41 • Number of events 125
|
|
Blood and lymphatic system disorders
FEBRILE NEUTROPENIA
|
7.3%
3/41 • Number of events 4
|
|
General disorders
FEVER
|
19.5%
8/41 • Number of events 12
|
|
Vascular disorders
FLUSHING
|
12.2%
5/41 • Number of events 12
|
|
Gastrointestinal disorders
GASTROESOPHAGEAL REFLUX DISEASE
|
7.3%
3/41 • Number of events 12
|
|
Gastrointestinal disorders
GASTROINTESTINAL HEMORRHAGE
|
9.8%
4/41 • Number of events 5
|
|
Nervous system disorders
HEADACHE
|
31.7%
13/41 • Number of events 28
|
|
Vascular disorders
HOT FLASHES
|
7.3%
3/41 • Number of events 6
|
|
Metabolism and nutrition disorders
HYPERGLYCEMIA
|
9.8%
4/41 • Number of events 12
|
|
Vascular disorders
HYPERTENSION
|
17.1%
7/41 • Number of events 18
|
|
Metabolism and nutrition disorders
HYPOCALCEMIA
|
7.3%
3/41 • Number of events 4
|
|
Metabolism and nutrition disorders
HYPOKALEMIA
|
9.8%
4/41 • Number of events 4
|
|
Metabolism and nutrition disorders
HYPOMAGNESEMIA
|
7.3%
3/41 • Number of events 4
|
|
Psychiatric disorders
INSOMNIA
|
34.1%
14/41 • Number of events 42
|
|
Blood and lymphatic system disorders
LEUKOPENIA
|
75.6%
31/41 • Number of events 106
|
|
Nervous system disorders
MEMORY IMPAIRMENT
|
7.3%
3/41 • Number of events 6
|
|
Gastrointestinal disorders
MUCOSITIS
|
39.0%
16/41 • Number of events 29
|
|
Musculoskeletal and connective tissue disorders
MYALGIA
|
24.4%
10/41 • Number of events 31
|
|
Skin and subcutaneous tissue disorders
NAIL DISCOLORATION
|
7.3%
3/41 • Number of events 4
|
|
Respiratory, thoracic and mediastinal disorders
NASAL CONGESTION
|
12.2%
5/41 • Number of events 8
|
|
Respiratory, thoracic and mediastinal disorders
NASAL DRAINAGE
|
12.2%
5/41 • Number of events 7
|
|
Gastrointestinal disorders
NAUSEA
|
78.0%
32/41 • Number of events 93
|
|
Musculoskeletal and connective tissue disorders
NECK PAIN
|
7.3%
3/41 • Number of events 3
|
|
Blood and lymphatic system disorders
NEUTROPENIA
|
92.7%
38/41 • Number of events 132
|
|
Gastrointestinal disorders
ORAL PAIN
|
17.1%
7/41 • Number of events 9
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
7.3%
3/41 • Number of events 22
|
|
Nervous system disorders
PERIPHERAL NEUROPATHY
|
43.9%
18/41 • Number of events 56
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
14.6%
6/41 • Number of events 10
|
|
General disorders
Pain
|
22.0%
9/41 • Number of events 10
|
|
Skin and subcutaneous tissue disorders
RASH
|
26.8%
11/41 • Number of events 28
|
|
Skin and subcutaneous tissue disorders
SCALP PAIN
|
7.3%
3/41 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
SINUSITIS
|
9.8%
4/41 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
SKIN HYPERPIGMENTATION
|
7.3%
3/41 • Number of events 5
|
|
Respiratory, thoracic and mediastinal disorders
SORE THROAT
|
12.2%
5/41 • Number of events 6
|
|
Nervous system disorders
TASTE ALTERATION
|
39.0%
16/41 • Number of events 55
|
|
Gastrointestinal disorders
THROAT PAIN
|
7.3%
3/41 • Number of events 4
|
|
Blood and lymphatic system disorders
THROMBOCYTOPENIA
|
78.0%
32/41 • Number of events 107
|
|
Vascular disorders
THROMBOEMBOLIC EVENT
|
7.3%
3/41 • Number of events 3
|
|
Gastrointestinal disorders
VOMITING
|
19.5%
8/41 • Number of events 18
|
|
Investigations
WEIGHT LOSS
|
7.3%
3/41 • Number of events 6
|
|
Injury, poisoning and procedural complications
WOUND COMPLICATION
|
9.8%
4/41 • Number of events 8
|
Additional Information
John D. Hainsworth, MD
Sarah Cannon Research Institute
Phone: 1-877-691-7274
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor can review/embargo results communications prior to public release for a period that is \>60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites
- Publication restrictions are in place
Restriction type: OTHER