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

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

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

Sponsors & Collaborators

• AstraZeneca

  collaborator INDUSTRY

• Hoosier Cancer Research Network

  collaborator OTHER

• Noah Hahn, M.D.

  lead OTHER

Principal Investigators

• Noah M. Hahn, MD · Hoosier Cancer Research Network

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2017-11-21

Primary Completion

2026-12-31

Completion

2027-12-31

FDA Drug

Yes

Countries

• United States

Study Locations