NCT03317158

Modern Immunotherapy in BCG-Unresponsive, BCG-Relapsing and High Risk BCG-Naive Non-Muscle Invasive Urothelial Carcinoma of the Bladder

PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-Unresponsive, BCG-RelaPsing, and High-Risk BCG-Naive Non-muscle Invasive UroThelial Carcinoma of the BLADDER

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 55 (estimated)
• Sponsor: Noah Hahn, M.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Upon successful screening and registration, enrollment to durvalumab monotherapy (cohort 1) will begin. If DLT criteria outlined in the protocol are exceeded with durvalumab monotherapy (cohort 1), the study will close. Provided the safety of durvalumab monotherapy is established, enrollment to combination regimen cohorts will proceed. Cohorts will simultaneously enroll in parallel to each other with patients assigned to cohorts based on patient slot availability and study site choice of radiation arm participation. Patient assignment to future phase 1 arms would proceed similarly. Within BCG-containing cohorts, treatment will begin at full-dose BCG. If DLT criteria outlined in Section 5.1.4 are exceeded with full-dose BCG, a one level dose reduction of BCG will be implemented. If DLT criteria outlined in Section 5.1.4 are exceeded with reduced-dose BCG, the BCG-containing cohort will not proceed to Phase 2 of the study. Similarly, if DLT criteria outlined in Section 5.1.4 are exceeded within non-BCG containing cohorts, the non-BCG containing cohort will not proceed to phase 2 of the study. Due to the prolonged half-life of antibody therapies, no dose adjustments are planned for durvalumab in any of the cohorts.

Conditions

• Urothelial Carcinoma
• Bladder Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab (Cohort 1-3)	Durvalumab 1120 mg intravenously Day 1 every 21 days x 8 cycles.
RADIATION	External Beam Radiotherapy (EBRT)	EBRT 6 Gy x 3; Cycle 1 Day 1, 3, and 5
BIOLOGICAL	Bacillus Calmette-Guérin (BCG)	Dose level 0 (starting dose) = Full-dose Dose level-1 = 1/3rd-dose BCG. Dose level -1 is expected to be utilized during the phase II portion of the study due to the ongoing and persistent shortage of BCG in the US.
DRUG	Gemcitabine	Gemcitabine 1000 mg intravesical weekly (+/- 2 days) x 6 doses
DRUG	Docetaxel	Docetaxel 37.5 mg intravesical weekly (+/- 2 days) x 6 doses.
BIOLOGICAL	Tremelimumab	Tremelimumab 75 mg intravenously Day 1 (+/- 2 days) every 28 days x 4 cycles.
DRUG	Durvalumab (Cohort 4/5)	Durvalumab 1500 mg intravenously Day 1 (+/- 2 days) every 28 days x 6 cycles.
OTHER	To be determined	Other regimens to be determined

Timeline

• Start date: 2017-11-21
• Primary completion: 2026-12-31
• Completion: 2027-12-31
• First posted: 2017-10-23
• Last updated: 2026-04-15

Locations

12 sites across 1 country: United States

Regulatory

• FDA-regulated drug study