Improve Checkpoint-blockade Response in Advanced Urothelial Cancer

Sponsor
The Netherlands Cancer Institute
Study ID
NCT03871036
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Tremelimumab — DRUG
    See experimental arm description for more details.
  • Durvalumab — DRUG
    See experimental arm description for more details.
  • Paclitaxel — DRUG
    See experimental arm description for more details.

Study Details

This trial will include metastatic urothelial carcinoma patients who progressed during or after treatment with anti-PD(L)1 therapy and have been treated by a platinum-containing regimen, or are cisplatin-ineligible. Patients will receive either paclitaxel in combination with durvalumab (anti-PDL-1) and a single dose (300 mg) of tremelimumab (anti-CTLA4), or paclitaxel with only a high dose of tremelimumab (750 mg). Tremelimumab (750 mg), without paclitaxel will be used as a comparison arm. A run-in safety phase will be followed by a non-comparative 3-arm randomized study with a Simon's 2-stage optimal design.

Key Dates

Start date
May 1, 2019
Status verified
Mar 2025
Primary completion
Sep 7, 2023
Completion
Jan 15, 2025

Study Design

Enrollment
53 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Tremelimumab 75 (R1)
    Run-in phase-1 (R1): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
  • Experimental: Tremelimumab 225 (R2)
    Run-in phase-2 (R2): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 225 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
  • Experimental: Tremelimumab vs Tremelimumab+Durvalumab (R3)
    Run-in phase-3 (R3): n=2 x 3 patients will be randomized over 2 arms: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45 OR * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 75 mg on day 1 of cycles 2-5 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
  • Experimental: Tremelimumab 300 (R4)
    Run-in phase-4 (R4): n=3 patients will be treated with: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
  • Experimental: Tremelimumab 750 (A)
    Arm A: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 750 mg on day 1 of cycles 2-6 and then every 12 weeks until week 45
  • Experimental: Tremelimumab+Durvalumab (B)
    Arm B: * paclitaxel 70 mg/m2 on day 1, 8, 15 of cycles 1-6 * tremelimumab 300 mg once on day 1 of cycle 2 * durvalumab 1500 mg on day 1 of cycles 2-12, every four weeks (until week 49)
  • Experimental: Tremelimumab without paclitaxel (C)
    Arm C (control arm): • tremelimumab 750 mg on day 1 of cycles 1-5 and then every 12 weeks until week 41

Primary Outcome Measure

Overall response rate (ORR), defined as the proportion of participants whose confirmed best overall response is either a PR or CR after treatment with paclitaxel and a high dose of tremelimumab based upon the RECIST v1.1 guidelines. [ Time Frame: Final ORR will be determined after the confirmatory scan of the last patient, which is scheduled up to 21 weeks after start of treatment of the final patient ]

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