Neoadjuvant Pembrolizumab in Combination With Gemcitabine Therapy in Cis-eligible/Ineligible UC Subjects

Part of paid clinical trials in Indianapolis, Indiana.

Sponsor
Jason R. Brown
Study ID
NCT02365766
Phase
PHASE1/PHASE2
Status
Completed

Conditions

Eligibility Criteria

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

Interventions

  • Pembrolizumab — DRUG
    In this dose-finding cohort, pembrolizumab (MK-3475) will be administered (cisplatin-eligible patients only) at starting dose 200mg IV every 21 days for 4 cycles to determine RP2D. Once MTD is established in phase Ib, pembrolizumab will be administered on phase II cohorts I and II at RP2D every 21 days for 5 cycles.
  • Gemcitabine — DRUG
    For cisplatin-eligible patients on phase Ib and phase II cohort 1, gemcitabine 1000mg/m2 IV, D1 and D8 every 21 days for 4 cycles. For cisplatin-ineligible patients on phase II cohort II, gemcitabine 1000mg/m2 will be administered D1, D8 and D15 every 28 days for 3 cycles.
  • Cisplatin — DRUG
    For cisplatin-eligible patients, cisplatin 70mg/m2 IV will be administered D1 every 21 days for 4 cycles.
  • Consolidative Surgery — PROCEDURE
    Following completion of treatment, subjects will then have surgery to remove their primary tumor within 2-7 weeks after their last dose of neoadjuvant therapy.

Study Details

This is a pre-surgical study involving subjects with muscle invasive bladder cancer, or urothelial cancer, who are candidates for neoadjuvant therapy. It is is a two-part trial with a one-arm phase Ib portion followed by a two-arm phase II portion. The study treatment is stratified into two cohorts based on cisplatin eligibility.

Key Dates

Start date
May 27, 2015
Status verified
Feb 2025
Primary completion
Aug 1, 2020
Completion
Feb 23, 2024

Study Design

Enrollment
83 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A - Phase 1b Dose Finding Cohort:
    Cisplatin-eligible subjects will receive pembrolizumab at starting dose of 200mg (dose level 0), and/or 120mg (dose level -1) in combination with gemcitabine and cisplatin. The MTD will be the highest pembrolizumab dose level in combination with gemcitabine/cisplatin every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days). Once the MTD is established, this portion of the study will close and the phase II will open to cohorts I and II at the recommended phase II dose (RP2D).
  • Experimental: Arm B - Phase II Cohort I:
    Cisplatin-eligible subjects receive gemcitabine/cisplatin every 21 days, repeated for 4 cycles. (Subjects with Ccr of 50-59 mL/min must follow split dosing of cisplatin over two days) . Pembrolizumab at RP2D is given every 21 days for 5 doses starting C1D8. Note: the last dose of pembrolizumab falls on what would be day 8 of a 5th 'chemo' cycle, however gemcitabine/cisplatin is NOT GIVEN. Subjects will then have consolidative surgery to remove their primary tumor within 2-7 weeks after their last dose of neoadjuvant therapy.
  • Experimental: Arm C - Phase II Cohort II:
    Cisplatin-ineligible subjects receive gemcitabine every week every 28 days for 3 cycles. Pembrolizumab at RP2D is given every 21 days for 5 doses starting C1D8. NOTE: due to the timing of gemcitabine cycles every 4 weeks, and every 3-week dosing of pembrolizumab, there are two doses of pembrolizumab given during cycle 2: D1 and D22. Additionally, the last dose of pembrolizumab falls on what would be D8 of a 4th 'chemo' cycle; however gemcitabine is NOT GIVEN. Subjects will then have consolidative surgery to remove their primary tumor within 2-7 weeks after their last dose of neoadjuvant therapy.

Primary Outcome Measure

Phase Ib: Safety of Pembrolizumab in Combination With Gemcitabine-Cisplatin [ Time Frame: Up to 4 weeks ]

Locations (9)

FacilityCityStateZIPSite coordinators
Community Regional Cancer CareIndianapolisIndiana46256-
Indiana University Melvin and Bren Simon Cancer CenterIndianapolisIndiana46202-
IU Health Central Indiana Cancer CenterIndianapolisIndiana46219-
St. Vincent HospitalIndianapolisIndiana46260-
Washington University: Siteman Cancer CenterSt LouisMissouri63110-
University of New Mexico Cancer CenterAlbuquerqueNew Mexico87106-
University Hospitals Seidman Cancer CenterClevelandOhio44106-
Thomas Jefferson University: Kimmel Cancer CenterPhiladelphiaPennsylvania19107-
Virginia Oncology AssociatesNorfolkVirginia23502-

Related coverage on Hipa.ai

Find similar trials in Indianapolis, IN

By condition
Bladder cancer
By specialty
OncologyUrology
By research site
Community Regional Cancer Care· Indianapolis, INIndiana University Melvin and Bren Simon Cancer Center· Indianapolis, INIU Health Central Indiana Cancer Center· Indianapolis, INSt. Vincent Hospital· Indianapolis, INWashington University: Siteman Cancer Center· St Louis, MOUniversity of New Mexico Cancer Center· Albuquerque, NM

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