NCT03150836

Radiation Therapy and Durvalumab, With or Without Tremelimumab, in Patients With Bladder Cancer

Multi-Institutional Phase II Study of Radiation Therapy and Anti-PD-L1 Checkpoint Inhibition (Durvalumab) With or Without Anti-CTLA-4 Inhibition (Tremelimumab) in Patients With Unresectable, Muscle-Invasive or Metastatic Urothelial Bladder Cancer That Are Ineligible or Refusing Chemotherapy

• Status: Withdrawn
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Terence Friedlander, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a multi-site, randomized, prospective, open-label phase II study. Patients in this study will have localized (cT3-cT4), or metastatic bladder cancer with a symptomatic, intact primary bladder tumor. In this study, patients will undergo stereotactic body radiation therapy (SBRT) to the bladder tumor and will receive durvalumab with or without tremelimumab.

Detailed description

The study will commence with a safety lead-in phase at UCSF in which 6 patients are accrued to Regimen A1 (RT + durvalumab). If this is not tolerated then an alternative Regimen A2, containing a lower total radiation dose will accrue 6 patients. If either A1 or A2 is tolerated then patients will be accrued to Regimen B1 (durvalumab, tremelimumab x 2 doses, and RT dose determined from Regimen A) following a 3+3 design for safety. If Regimen B1 is not tolerated an alternative Regimen B2 (durvalumab, tremelimumab x 1 dose, and RT dose determined from regimen A) will accrue following a 3+3 design for safety. After the safety lead-in for each group is completed, an expansion cohort will accrue patients. In this expansion cohort, patients will be randomized 1:1 to be treated with either regimen A or regimen B dose selected from the safety lead-in stratified by patient population (localized patients and metastatic patients).

Conditions

• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab	All participants will receive durvalumab 1500 mg via IV infusion every 4 weeks for up to 13 doses.
DRUG	Tremelimumab	Participants receiving Regimen B (safety lead-in or expansion cohort) will be administered tremelimumab 75 mg via IV infusion every 4 weeks for 1 cycle or 2 cycles.
RADIATION	Radiation Therapy	In all arms of the study, participants will receive 5 fractions of radiation. The radiation dose will either be 6.6 Gy for a total dose of 33 Gy, or 6.0 Gy for a total dose of 30 Gy.

Timeline

• Start date: 2017-10-01
• Primary completion: 2021-09-01
• Completion: 2024-09-01
• First posted: 2017-05-12
• Last updated: 2017-10-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study