A Phase II Study of Atezolizumab in Combination With Cisplatin + Gemcitabine Before Surgery to Remove the Bladder Cancer

NCT02989584 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 16-1428
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 11

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.

Conditions

Bladder Cancer; Metastatic Bladder Cancer; Urothelial Carcinoma

Keywords

bladder cancer; metastatic bladder cancer; atezolizumab; urothelial carcinoma

Outcome Measures

Primary Outcomes (1)

• Test the safety of atezolizumab in combination with gemcitabine/cisplatin as assessed by dose limiting toxicity rate.

  CTCAE version 4.0 will be used for all patients on this trial for evaluation of toxicities during systemic therapy.

  Participants will be followed for survival until 5 years from treatment completion or until disease recurrence/progression.

Secondary Outcomes (1)

• Relapse-Free Survival

  3 years

Study Arms (1)

Atezolizumab, Gemcitabine, Cisplatin

EXPERIMENTAL

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.

Drug: Atezolizumab; Drug: Gemcitabine; Drug: Cisplatin

Interventions

Atezolizumab DRUG

Atezolizumab, Gemcitabine, Cisplatin

Gemcitabine DRUG

Atezolizumab, Gemcitabine, Cisplatin

Cisplatin DRUG

Atezolizumab, Gemcitabine, Cisplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Alkaline phosphatase ≤ 2.5 x ULN for the institution
• For patients in the metastatic cohort with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN
• If female of childbearing potential, urine pregnancy test is negative.
• INR and aPTT ≤ 1.5 x ULN if not on therapeutic anticoagulation. Patients receiving therapeutic anticoagulation should be on a stable dose.
• Phase I Cohort

You may not qualify if:

• 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 ≥ 2. 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
• Pregnancy, lactation, or breast-feeding. Patients must be surgically sterile, postmenopausal, or must agree to use effective contraception during the period of therapy and for 5 months after the last dose of atezolizumab. The definition of effective contraception will be based on the judgment of the principal investigator or a designated associate. Male patients must be surgically sterile or agree to use effective contraception. Male patients will be encouraged to notify the study team if their female partner becomes pregnant while on study.
• History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, systemic vasculitis, or glomerulonephritis.
• Patients with history of autoimmune related hypothyroidism on stable dose of thyroid replacement hormone may be eligible for this study
• Patients with controlled Type I diabetes mellitus on a stable dose of insulin may be eligible for this study
• History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (11)

Hartford Healthcare Cancer Institute @ Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

New York University

New York, New York, 10010, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103, United States

Location

Related Publications (1)

• Funt SA, Lattanzi M, Whiting K, Al-Ahmadie H, Quinlan C, Teo MY, Lee CH, Aggen D, Zimmerman D, McHugh D, Apollo A, Durdin TD, Truong H, Kamradt J, Khalil M, Lash B, Ostrovnaya I, McCoy AS, Hettich G, Regazzi A, Jihad M, Ratna N, Boswell A, Francese K, Yang Y, Folefac E, Herr HW, Donat SM, Pietzak E, Cha EK, Donahue TF, Goh AC, Huang WC, Bajorin DF, Iyer G, Bochner BH, Balar AV, Mortazavi A, Rosenberg JE. Neoadjuvant Atezolizumab With Gemcitabine and Cisplatin in Patients With Muscle-Invasive Bladder Cancer: A Multicenter, Single-Arm, Phase II Trial. J Clin Oncol. 2022 Apr 20;40(12):1312-1322. doi: 10.1200/JCO.21.01485. Epub 2022 Jan 28.

  PMID: 35089812 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

atezolizumab; Gemcitabine; Cisplatin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Samuel Funt, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 12, 2016
• Study Start: December 20, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 7, 2026

Record last verified: 2026-01

Locations

US (11)