NCT02451423

Neoadjuvant Atezolizumab in Localized Bladder Cancer

Phase II Study of Neoadjuvant Atezolizumab-based Immunotherapy for Patients With Urothelial Carcinoma (NEBULA)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Lawrence Fong · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial studies the best dose of atezolizumab in treating patients with bladder cancer that has not spread to other places in the body. Immunotherapy with monoclonal antibodies may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. To assess the intratumoral immune response associated with increasing numbers of atezolizumab (MPDL3280A) treatments. (Multi-dose cohorts, Cohort A). II. To assess the anti-tumor activity of MPDL3280A as determined by the pathologic T0 rate (pT0) at the time of cystectomy. (Expansion cohorts, Cohort A). SECONDARY OBJECTIVES: I. To evaluate the safety and feasibility of administering up to 3 cycles of atezolizumab pre-operatively to patients with resectable urothelial bladder cancer (Multi-dose cohorts). II. To assess the anti--tumor activity of neoadjuvant treatment as determined by the pathologic partial response (\< pT2N0) assessed at the time of radical cystectomy (Expansion cohorts). III. To determine the 2-year relapse-free survival (RFS) rate and median RFS from time of radical cystectomy in patients treated with neoadjuvant therapy (Expansion cohorts). IV. To determine the 2-year overall survival (OS) and median OS from time of radical cystectomy in patients treated with neoadjuvant therapy (Expansion cohorts). V. To assess the intratumoral immune response of neoadjuvant by comparing pre-treatment transurethral resection of bladder tumor (TURBT) with post-treatment cystectomy tumor specimens (Expansion cohorts). EXPLORATORY (CORRELATIVE) OBJECTIVES: I. To assess for tumor-based biomarkers of response and resistance to this combination therapy using single-cell RNA sequencing (scRNA-seq) and high-dimensional flow cytometry. II. To assess the presence of antigen-specific immune responses to a broad panel of candidate tumor antigens. OUTLINE: This is a dose-escalation study of atezolizumab. COHORT A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 3 doses prior to cystectomy in the absence of disease progression or unacceptable toxicity. COHORT B: Cohort B was never opened for enrollment. After all neoadjuvant study therapy is administered, each subject will undergo cystectomy to evaluate pathologic response to treatment and for immunologic characterization in the resected tissue. Serum and urine will be obtained as well to characterize circulating immune responses. After completion of study treatment, patients are followed for up every 4 weeks for 12 weeks and then every 12 weeks for up to 2 years.

Conditions

• Carcinoma, Transitional Cell

Interventions

Type	Name	Description
DRUG	Atezolizumab	1200 mg Given IV

Timeline

• Start date: 2016-03-29
• Primary completion: 2023-03-31
• Completion: 2023-03-31
• First posted: 2015-05-22
• Last updated: 2024-05-31
• Results posted: 2024-05-31

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study