Trial Outcomes & Findings for Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma (NCT NCT00588666)

Last Updated: 2016-01-22

Results Overview

Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee \[JNCI, 92(3):205-216, 2000\]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

51 participants

Primary outcome timeframe

3 years

Results posted on

2016-01-22

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Overall Study STARTED	51
Overall Study COMPLETED	47
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Overall Study Adverse Event	4

Baseline Characteristics

Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment n=51 Participants Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=99 Participants
Age, Categorical >=65 years	36 Participants n=99 Participants
Sex: Female, Male Female	14 Participants n=99 Participants
Sex: Female, Male Male	37 Participants n=99 Participants
Region of Enrollment United States	51 participants n=99 Participants

PRIMARY outcome

Timeframe: 3 years

Outcome measures

Outcome measures
Measure	Treatment n=47 Participants Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Evaluate the Time to Disease Progression Time to Progression	6.5 months Interval 4.7 to 7.8
Evaluate the Time to Disease Progression Overall Survival	13.9 months Interval 11.9 to 18.1

SECONDARY outcome

Timeframe: 3 years

Outcome measures

Outcome measures
Measure	Treatment n=47 Participants Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.	49 percentage of participants

Adverse Events

Treatment

Serious events: 29 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment n=51 participants at risk Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
Cardiac disorders Myocardial ischemia	2.0% 1/51 • Number of events 1
Hepatobiliary disorders Cholecystitis	2.0% 1/51 • Number of events 1
Gastrointestinal disorders Constipation	3.9% 2/51 • Number of events 2
General disorders Death	2.0% 1/51 • Number of events 1
Gastrointestinal disorders Dysphagia	2.0% 1/51 • Number of events 1
General disorders Fatigue	2.0% 1/51 • Number of events 1
Blood and lymphatic system disorders Febrile neutropenia	3.9% 2/51 • Number of events 2
Musculoskeletal and connective tissue disorders Fracture	2.0% 1/51 • Number of events 1
Blood and lymphatic system disorders Anemia	2.0% 1/51 • Number of events 1
General disorders Hemorrhage/Bleeding, other	2.0% 1/51 • Number of events 1
Hepatobiliary disorders Hepatobiliary disease	2.0% 1/51 • Number of events 1
Infections and infestations Abdominal infection	2.0% 1/51 • Number of events 1
Respiratory, thoracic and mediastinal disorders Pneumonia	2.0% 1/51 • Number of events 1
Infections and infestations Bladder infection	3.9% 2/51 • Number of events 2
Infections and infestations Tooth infection	2.0% 1/51 • Number of events 1
Infections and infestations Urinary tract infection	2.0% 1/51 • Number of events 1
Investigations White blood cell decreased	2.0% 1/51 • Number of events 1
Investigations Lipase increased	2.0% 1/51 • Number of events 1
Injury, poisoning and procedural complications Injury, poisoning, and procedural complications-other, specify-device complication	3.9% 2/51 • Number of events 2
Musculoskeletal and connective tissue disorders Muscle weakness	2.0% 1/51 • Number of events 1
Gastrointestinal disorders Nausea	2.0% 1/51 • Number of events 1
Investigations Neutrophil count decrease	2.0% 1/51 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/51 • Number of events 1
General disorders Chest pain	2.0% 1/51 • Number of events 1
Musculoskeletal and connective tissue disorders Neck pain	2.0% 1/51 • Number of events 1
Investigations Platelet count decrease	3.9% 2/51 • Number of events 3
Renal and urinary disorders Renal and urinary disorders-other, specify-Renal failure	5.9% 3/51 • Number of events 3
Nervous system disorders Syncope	2.0% 1/51 • Number of events 1
Injury, poisoning and procedural complications Vascular access complication	2.0% 1/51 • Number of events 1
Vascular disorders Thrombosis/thrombus/embolism	15.7% 8/51 • Number of events 8
Gastrointestinal disorders Duodenal ulcer	2.0% 1/51 • Number of events 1
Gastrointestinal disorders Vomiting	2.0% 1/51 • Number of events 1

Other adverse events

Other adverse events
Measure	Treatment n=51 participants at risk Bevacizumab, Carboplatin, Gemcitabine: Patients will initially receive bevacizumab 10 mg/kg followed by a 2 week treatment-free interval. Treatment will then begin with combination therapy. Gemcitabine 1000 mg/m2 will be administered intravenously on day 1 and 8 and carboplatin AUC 4.5 on day 1 with treatment recycled every 21 days. Bevacizumab will be administered at a dose of 15 mg/kg on day 1 of each 21-day cycle. Restaging evaluations will be performed after every 3 cycles of treatment (approximately 9 weeks). Patients will receive a total of 6 cycles of chemotherapy unless disease progression or unacceptable toxicity occurs. Patients who achieve stable disease, a partial response, or a complete response after completion of 6 cycles, will be eligible to continue bevacizumab at the same dose and schedule until disease progression for a maximum of 18 additional doses.
General disorders Fatigue	21.6% 11/51 • Number of events 30
Gastrointestinal disorders Nausea	5.9% 3/51 • Number of events 6
Vascular disorders Thrombosis/thrombus/embolism	7.8% 4/51 • Number of events 4
Investigations Weight loss	7.8% 4/51 • Number of events 6

Additional Information

Dr. Dean Bajorin

Memorial Sloan Kettering Cancer Center

Phone: 646-422-4333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place