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

Conditions

• Bladder Cancer
• Urothelial Carcinoma

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Durvalumab (Cohort 1-3) — DRUG
  Durvalumab 1120 mg intravenously Day 1 every 21 days x 8 cycles.
• External Beam Radiotherapy (EBRT) — RADIATION
  EBRT 6 Gy x 3; Cycle 1 Day 1, 3, and 5
• Bacillus Calmette-Guérin (BCG) — BIOLOGICAL
  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.
• Gemcitabine — DRUG
  Gemcitabine 1000 mg intravesical weekly (+/- 2 days) x 6 doses
• Docetaxel — DRUG
  Docetaxel 37.5 mg intravesical weekly (+/- 2 days) x 6 doses.
• Tremelimumab — BIOLOGICAL
  Tremelimumab 75 mg intravenously Day 1 (+/- 2 days) every 28 days x 4 cycles.
• Durvalumab (Cohort 4/5) — DRUG
  Durvalumab 1500 mg intravenously Day 1 (+/- 2 days) every 28 days x 6 cycles.
• To be determined — OTHER
  Other regimens to be determined

Study Details

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.

Key Dates

Start date

Nov 21, 2017

Status verified

Apr 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2027

Study Design

Enrollment

55 participants (estimated)

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Arms

• Experimental: Phase 1: Cohort 1
  Durvalumab monotherapy
• Experimental: Phase 1: Cohort 2
  Durvalumab plus BCG
• Experimental: Phase 1: Cohort 3
  Durvalumab plus External Beam Radiotherapy (EBRT) (BCG re-treatment) - Cross-over to Durvalumab Monotherapy
• Experimental: Phase 1: Cohort 4
  Durvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.
• Experimental: Phase 1: Cohort 5
  NOTE: Cohort 5 was abandoned prior to any patients enrolled. Durvalumab + Tremelimumab + Gem/Doc The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments. For the intravenous medications, durvalumab should be administered first followed by tremelimumab.
• Experimental: Phase 1: Cohort 6
  Additional Regimens (to be determined)
• Experimental: Phase 2: Cohort 4 Expansion
  Durvalumab + Gemcitabine/Intravesical Docetaxel (Gem/Doc) The sequence of administration is flexible to allow for scheduling of both the infusion and intravesical treatments.

Primary Outcome Measure

Phase 1: Determine the recommended phase 2 dose (RP2D) from BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) [ Time Frame: 6 months ]

Central Contacts

• Noah Hahn, MD
  443-287-2886
  [email protected]
• LeaEtta Hyer
  317-634-5842
  [email protected]

Locations (12)

Find similar trials in Phoenix, AZ

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