Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer
Cisplatin is a very important agent for the treatment of TCC as it has a single agent response rate of approximately 15%. However, it has been most important as a part of combination chemotherapy, MVAC initially and now in combination with gemcitabine. Single agent gemcitabine has demonstrated an overall response rate (ORR) of approximately 25%, including some complete responses (CR), with minimal toxicity in patients with advanced bladder cancer. Bevacizumab, a murine anti-human VEGF monoclonal antibody, has been advanced for use in combination with cytotoxic chemotherapy to delay time to disease progression in patients with metastatic solid tumors.
This trial is designed to further assess the efficacy, safety and tolerability of this regimen in this patient population.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Trial of Cisplatin, Gemcitabine and Bevacizumab in Combination for Metastatic Transitional Cell Cancer: Hoosier Oncology Group GU04-75|
- - To determine the progression free survival of patients with metastatic transitional cell cancer treated with cisplatin, gemcitabine and bevacizumab. [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To estimate the time to event efficacy variables, including duration of response for responding patients, time to treatment failure and overall survival time [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- To characterize the quantitative and qualitative toxicities of cisplatin gemcitabine and bevacizumab in this patient population. [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
- To estimate rate of partial response (PR), complete response (CR) and overall response (PR plus CR). [ Time Frame: 36 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2005|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Active Comparator: 1
Cisplatin + Gemcitabine + Bevacizumab
Cisplatin 70 mg/m2, day 1Drug: Gemcitabine
Gemcitabine 1250 mg/m2, day 1 and 8Drug: Bevacizumab
Bevacizumab 15mg/kg, day 1
OUTLINE: This is a multi-center study.
- Cisplatin 70 mg/m2 Day 1
- Gemcitabine 1250 mg/m2 Day 1 and 8
- Bevacizumab 15 mg/kg Day 1
Review toxicity every cycle (every 3 weeks) Review for radiographic response every 2 cycles (every six weeks)
Progressive disease = off protocol therapy
Patients will be treated for up to a maximum of 8 cycles of cisplatin and gemcitabine (24 weeks of therapy). If a patient has not progressed by the end of 24 weeks (completion of cisplatin and gemcitabine), then patient will be treated with bevacizumab at 15 mg/kg every three weeks for a maximum of 12 months of bevacizumab therapy (since study entry).
If at any time patient has undue toxicity or progressive disease, patient will be removed from the study and followed until progression and for survival.
If the patient has Grade 3 or 4 neurotoxicity and/or the creatinine rises above 2.0, then the cisplatin will be discontinued and the patient continued on study and treated with gemcitabine and bevacizumab at the same dose and schedule.
ECOG Performance Status 0 or 1
- White blood cell count > 3000/mm3
- Absolute neutrophil count (ANC) > 1500 mm/3
- Platelet count > 100,000/mm3
- Hemoglobin > 8 g/dL (may be transfused or receive erythropoietin support to maintain or exceed this level).
- INR < 1.5
- No full dose/therapeutic anticoagulation with either low molecular weight heparin or unfractionated heparin or coumadin
- Total bilirubin of <1.5 mg/dL
- ALT <5 times upper limit of normal for subjects with documented liver metastases; <2.5 times the upper limit of normal for subjects without evidence of liver metastases.
- Serum creatinine of < 1.5 mg/dL.
- Urine protein:creatinine ratio < 1.0 at screening
- No history of myocardial infarction or stroke within the last 6 months
- No uncontrolled hypertension (blood pressure of >160 systolic and/or 110 diastolic mmHg on medication)
- No unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure
- No unstable symptomatic arrhythmia requiring medication (subjects with chronic atrial arrhythmia, i.e., atrial fibrillation or paroxysmal supraventricular tachycardia are eligible), or clinically significant peripheral vascular disease.
- Not specified
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637|
|Medical & Surgical Specialists, LLC|
|Galesburg, Illinois, United States, 61401|
|United States, Indiana|
|Oncology Hematology Associates of SW Indiana|
|Evansville, Indiana, United States, 47714|
|Fort Wayne Oncology & Hematology, Inc|
|Fort Wayne, Indiana, United States, 46815|
|Quality Cancer Center (MCGOP)|
|Indianapolis, Indiana, United States, 46202|
|Indiana University Cancer Center|
|Indianapolis, Indiana, United States, 46202|
|Arnett Cancer Care|
|Lafayette, Indiana, United States, 47904|
|Northern Indiana Cancer Research Consortium|
|South Bend, Indiana, United States, 46601|
|Terre Haute, Indiana, United States, 47804|
|United States, Missouri|
|Siteman Cancer Center|
|St. Louis, Missouri, United States, 63110|
|United States, Ohio|
|Oncology Hematology Care, Inc.|
|Cincinnati, Ohio, United States, 45242|
|Study Chair:||Christopher Sweeney, M.B.B.S.||Hoosier Oncology Group, LLC|