NCT02812420

Durvalumab and Tremelimumab in Treating Patients With Muscle-Invasive, High-Risk Urothelial Cancer That Cannot Be Treated With Cisplatin-Based Therapy Before Surgery

A Pilot Pre-Surgical Study Evaluating Anti-PD-L1 Antibody (Durvalumab) Plus Anti-CTLA-4 (Tremelimumab) in Patients With Muscle-Invasive, High-Risk Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Neoadjuvant Chemotherapy

• Status: Active Not Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This pilot phase I trial studies the side effects of durvalumab and tremelimumab in treating patients with muscle-invasive, high-risk urothelial cancer that cannot be treated with cisplatin-based therapy before surgery. Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies. SECONDARY OBJECTIVES: I. To assess immunologic/molecular responses (e.g. peripheral blood cluster of differentiation \[CD\] 4+inducible T-cell co-stimulator \[ICOS\]+ T cells) to durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer who are ineligible for neoadjuvant cisplatin-containing chemotherapies. II. To evaluate pathologic T0 rate after neoadjuvant treatment with durvalumab and tremelimumab in patients with muscle-invasive, high-risk bladder cancer comparing to historical data (about 10% in patients with high-risk disease). III. To evaluate relapse-free survival (RFS) and overall survival (OS). OUTLINE: Patients receive tremelimumab intravenously (IV) over 1 hour and durvalumab IV over 1 hour on day 1 of weeks 1 and 4. Beginning 4-6 weeks after the last infusion, patients undergo cystectomy with pelvic lymph node dissection surgery. After completion of study treatment, patients are followed up at 90 days, and then every 3 months for up 1 year.

Conditions

• Hydronephrosis
• Infiltrating Bladder Urothelial Carcinoma Sarcomatoid Variant
• Infiltrating Bladder Urothelial Carcinoma, Micropapillary Variant
• Infiltrating Bladder Urothelial Carcinoma, Plasmacytoid Variant
• Infiltrating Renal Pelvis Urothelial Carcinoma, Sarcomatoid Variant
• Renal Pelvis Urothelial Carcinoma
• Stage II Bladder Urothelial Carcinoma AJCC v6 and v7
• Stage II Renal Pelvis Cancer AJCC v7
• Stage II Ureter Cancer AJCC v7
• Stage II Urethral Cancer AJCC v7
• Stage III Bladder Urothelial Carcinoma AJCC v6 and v7
• Stage III Renal Pelvis Cancer AJCC v7
• Stage III Ureter Cancer AJCC v7
• Stage III Urethral Cancer AJCC v7
• Stage IV Renal Pelvis Cancer AJCC v7
• Stage IV Ureter Cancer AJCC v7
• Stage IV Urethral Cancer AJCC v7
• Ureter Urothelial Carcinoma
• Urethral Urothelial Carcinoma

Interventions

Type	Name	Description
BIOLOGICAL	Durvalumab	Given IV
PROCEDURE	Therapeutic Conventional Surgery	Undergo cystectomy with pelvic lymph node dissection
BIOLOGICAL	Tremelimumab	Given IV

Timeline

• Start date: 2017-03-07
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2016-06-24
• Last updated: 2026-03-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study