Trial Outcomes & Findings for Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer (NCT NCT02412670)

Last Updated: 2023-07-10

Results Overview

Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

36 participants

Primary outcome timeframe

Assessed at nephroureterectomy or regional lymph node dissection (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Results posted on

2023-07-10

Participant Flow

The study was activated on April 1, 2015 and accrued its first patient on August 27, 2015. Arm A reached its accrual and was closed on May 31, 2017. Arm B was closed due to slow accrual on January 5, 2018.

Participant milestones

Participant milestones
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Overall Study STARTED	30	6
Overall Study Eligible and Treated	29	6
Overall Study COMPLETED	23	5
Overall Study NOT COMPLETED	7	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Overall Study Adverse Event	4	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	1	0
Overall Study Ineligible	1	0

Baseline Characteristics

Chemotherapy Before Surgery in Treating Patients With High Grade Upper Urinary Tract Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=29 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Total n=35 Participants Total of all reporting groups
Age, Continuous	65 years n=99 Participants	75 years n=107 Participants	66 years n=206 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	2 Participants n=107 Participants	8 Participants n=206 Participants
Sex: Female, Male Male	23 Participants n=99 Participants	4 Participants n=107 Participants	27 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	2 Participants n=107 Participants	2 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants n=99 Participants	4 Participants n=107 Participants	31 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants
Race (NIH/OMB) White	26 Participants n=99 Participants	4 Participants n=107 Participants	30 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	2 Participants n=107 Participants	3 Participants n=206 Participants

PRIMARY outcome

Timeframe: Assessed at nephroureterectomy or regional lymph node dissection (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Population: Eligible and treated patients

Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=29 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Complete Pathologic Response Rate	0.103 proportion of participants Interval 0.039 to 0.216	0.167 proportion of participants Interval 0.017 to 0.51

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years; and every 6 months for 3-5 years

Population: Eligible and treated patients who underwent radical nephro-ureterectomy and were rendered disease-free

Recurrence-free survival is defined as the time from the date of surgery to disease recurrence or death from any cause. Patients alive without documented recurrence will be censored at the date of last disease assessment.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=28 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=5 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Recurrence-free Survival	NA months Median was not reached. The upper and lower limits of the 90% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.	8.5 months Interval 3.3 to The upper limit of the 90% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, and every 6 months for 3-5 years

Population: Eligible and treated patients

Event-free survival is defined as the time from registration to the earliest occurrence of recurrence of any type, disease progression, new invasive primary cancer, or death from any cause. Disease progression will be assessed using RECIST 1.1. Disease progression is defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=29 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Event-free Survival	NA months Median was not reached. The upper and lower limits of the 90% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.	10.2 months Interval 7.1 to The upper limit of the 90% confidence interval was not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years, and every 6 months for 3-5 years

Population: Eligible and treated patients who underwent radical nephro-ureterectomy and were rendered disease-free

Bladder cancer-free survival was defined as the time from the date of surgery to the earlier of a return of bladder cancer or death from any cause. Patients alive without documented bladder cancer were censored at the date of last disease assessment.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=28 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=5 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Bladder Cancer-free Survival	NA months Median was not reached. The upper and lower limits of the 90% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.	NA months Median was not reached. The upper and lower limits of the 90% confidence interval were not calculable because an insufficient number of participants reached the event at the final time point for assessment.

SECONDARY outcome

Timeframe: Assessed every 3 months for 2 years

Population: Eligible and treated patients

Cancer-specific survival was defined as the time from registration to death due to cancer; deaths due to other causes are counted as competing events. Cancer-specific survival was analyzed using Gray's method and cumulative incidence of cancer-specific death at 24 months is reported.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=29 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Cumulative Incidence of Cancer-specific Death at 24 Months	0.09 proportion of patients died of cancer Interval 0.02 to 0.21	0.20 proportion of patients died of cancer Interval 0.01 to 0.56

SECONDARY outcome

Timeframe: Assessed at completion of chemotherapy; at 8 weeks for Arm A and 12 weeks for Arm B

Population: All patients with chemotherapy

Renal insufficiency is defined as CrCl \< 60 ml/min.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=30 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy	0.2 proportion of participants Interval 0.091 to 0.357	0.833 proportion of participants Interval 0.418 to 0.991

SECONDARY outcome

Timeframe: Assessed at completion of surgery (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Population: All patients who underwent radical nephro-ureterectomy

Renal insufficiency is defined as CrCl \< 60 ml/min.

Outcome measures

Outcome measures
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=29 Participants Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 Participants Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Proportion of Patients With Renal Insufficiency at Completion of Surgery	0.69 proportion of participants Interval 0.521 to 0.828	0.833 proportion of participants Interval 0.418 to 0.991

Adverse Events

Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)

Serious events: 7 serious events

Other events: 30 other events

Deaths: 2 deaths

Arm B (Gemcitabine, Carboplatin)

Serious events: 3 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin) n=30 participants at risk Patients receive methotrexate IV over 2-3 minutes, vinblastine IV, doxorubicin hydrochloride IV, and cisplatin IV over 4 hours on day 1. Pegfilgrastim at 6 mg is given once 24-48 hours after completion of chemotherapy. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.	Arm B (Gemcitabine, Carboplatin) n=6 participants at risk Patients receive gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8 and carboplatin IV over 30-60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients without metastatic disease undergo nephroureterectomy and lymph node dissection 21-60 days after completion of chemotherapy.
Blood and lymphatic system disorders Anemia	66.7% 20/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	83.3% 5/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
General disorders Fatigue	73.3% 22/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	83.3% 5/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Gastrointestinal disorders Nausea	76.7% 23/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	66.7% 4/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Gastrointestinal disorders Vomiting	20.0% 6/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	33.3% 2/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Investigations Creatinine increased	36.7% 11/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	33.3% 2/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Investigations Neutrophil count decreased	6.7% 2/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	33.3% 2/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Investigations Platelet count decreased	30.0% 9/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	50.0% 3/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Investigations White blood cell decreased	6.7% 2/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	50.0% 3/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.
Nervous system disorders Peripheral sensory neuropathy	13.3% 4/30 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.	0.00% 0/6 • Assessed every 2 weeks for arm A and every 3 weeks for arm B while on treatment and for 30 days after the end of treatment up to 5 years Serious adverse events are defined as treatment-related adverse events of grade 3 or higher. Other adverse events are treatment-related adverse events not included in the serious adverse events.

Additional Information

Study Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60