A Pilot Safety Study and Single Arm Phase II Study of Gemcitabine and Cisplatin With Atezolizumab (MPDL3280A) in Patients With Metastatic and Muscle Invasive Bladder Cancer, Respectively
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Bladder Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 54
- Locations
- 15
- Primary Endpoint
- Test the safety of atezolizumab in combination with gemcitabine/cisplatin as assessed by dose limiting toxicity rate.
- Status
- Active, Not Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The purpose of this study is to test the safety of the study drug, atezolizumab, when combined with the standard chemotherapy drugs, gemcitabine and cisplatin (or GC). This study will help researchers begin to understand whether combining GC with atezolizumab is better, the same, or worse than the usual approach of using GC alone.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years
- •ECOG Performance Status of 0 or 1
- •Required Initial Laboratory Values within 14 days of enrollment:
- •Absolute Neutrophil Count ≥ 1500 cells/mm\^3
- •Lymphocyte count ≥ 300/mm\^3
- •Platelets ≥ 100,000 cells/mm\^3
- •Hemoglobin ≥ 9.0 g/dL
- •Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution For patients with known Gilbert's disease: bilirubin ≤ 3 x ULN
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x ULN for the institution.
- •For patients in the metastatic cohort with documented liver or bone metastases: AST and/or ALT ≤ 5.0 x ULN
Exclusion Criteria
- •Evidence of NYHA functional class III or IV heart disease
- •Serious intercurrent medical or psychiatric illness, including serious active infection
- •Preexisting sensory grade ≥ 2 neuropathy
- •Preexisting grade ≥ 2 hearing loss
- •Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study. Transurethral resection or other urinary tract diagnostic procedures, excisional biopsy, or MediPort placement, are NOT defined as major surgical procedures.
- •Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, or transient ischemic attack
- •Ongoing cardiac dysrhythmias of NCI CTCAE Version 4.0 grade ≥
- •However, stable atrial fibrillation controlled medically or with a device (e.g. pacemaker) or prior ablation is allowed.
- •History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
- •Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. QOL, are allowed
Arms & Interventions
Atezolizumab, Gemcitabine, Cisplatin
This is a two phase study with a single study arm for each phase. For Phase 1: Following enrollment participants will be treated with combination therapy on a 21 day cycle x 6 cycles. Gemcitabine (1000 mg/m2 on Day 1 and Day 8), cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously. Phase 2: Following enrollment participants will be treated with a single dose of atezolizumab alone followed by combination therapy on a 21-day cycle x 4 cycles, followed by a single dose of atezolizumab alone. Gemcitabine 1000mg/m2, cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously.
Intervention: Atezolizumab
Atezolizumab, Gemcitabine, Cisplatin
This is a two phase study with a single study arm for each phase. For Phase 1: Following enrollment participants will be treated with combination therapy on a 21 day cycle x 6 cycles. Gemcitabine (1000 mg/m2 on Day 1 and Day 8), cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously. Phase 2: Following enrollment participants will be treated with a single dose of atezolizumab alone followed by combination therapy on a 21-day cycle x 4 cycles, followed by a single dose of atezolizumab alone. Gemcitabine 1000mg/m2, cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously.
Intervention: Gemcitabine
Atezolizumab, Gemcitabine, Cisplatin
This is a two phase study with a single study arm for each phase. For Phase 1: Following enrollment participants will be treated with combination therapy on a 21 day cycle x 6 cycles. Gemcitabine (1000 mg/m2 on Day 1 and Day 8), cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously. Phase 2: Following enrollment participants will be treated with a single dose of atezolizumab alone followed by combination therapy on a 21-day cycle x 4 cycles, followed by a single dose of atezolizumab alone. Gemcitabine 1000mg/m2, cisplatin (70 mg/m2 on Day 1), and atezolizumab (1200 mg on Day 8) will be administered intravenously.
Intervention: Cisplatin
Outcomes
Primary Outcomes
Test the safety of atezolizumab in combination with gemcitabine/cisplatin as assessed by dose limiting toxicity rate.
Time Frame: Participants will be followed for survival until 5 years from treatment completion or until disease recurrence/progression.
CTCAE version 4.0 will be used for all patients on this trial for evaluation of toxicities during systemic therapy.
Secondary Outcomes
- Relapse-Free Survival(3 years)