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

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.

Eligibility

Age range

18+ years

Sex

All

Healthy volunteers

No

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.

Locations (12)