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Purpose

This study is being done to see how well two drugs (enfortumab vedotin and pembrolizumab) work together as a bladder preservation approach to treat patients with muscle invasive bladder cancer. The study will compare these drugs to concurrent chemoradiotherapy that is usually used to treat this cancer (standard of care). The study will enroll patients with muscle-invasive bladder cancer (MIBC) who have cancer that has not spread outside the bladder.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Has histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology staged cT2-T4aN0M0 - Tissue comprising muscle-invasive urothelial cancer must be submitted for clinical staging at baseline - Eligible for and agree to receive chemoradiotherapy and one of the protocol-specified radiosensitizing chemotherapy regimens - Fit for systemic therapy and elect bladder preservation, including participants who are ineligible for or have elected not to undergo cystectomy - Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Exclusion Criteria

  • Advanced or metastatic disease (N+, M1), non-urothelial carcinoma, diffuse or multifocal CIS, urothelial carcinoma or histological variant at any site outside the urinary bladder within previous 24 months prior to randomization except Ta/T1/CIS of the upper urinary tract including renal pelvis and ureter if the participant had undergone complete nephrectomy - Has received any prior systemic treatment, chemoradiation, and/or radiation for MIBC or NMIBC - Prior pelvic radiation for any reason - Inadequate bladder function - Other active malignancies within 3 years prior to randomization - Previously treated with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs) - Previously treated with a PD(L)-1 inhibitor, defined as a PD-1 inhibitor or PD-L1 inhibitor - Uncontrolled diabetes - Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted - Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection - Received major surgery (defined as requiring general anesthesia and >24 hour inpatient hospitalization) within 4 weeks prior to randomization - Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin - Known genetic disorders associated with radiosensitivity (eg, ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi syndrome) - Active keratitis or corneal ulcerations - History of autoimmune disease that has required systemic treatment in the past 2 years - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan - Prior allogeneic stem cell or solid organ transplant - Received a live attenuated vaccine within 30 days prior to randomization

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
A randomized, controlled, parallel-group, multicenter, open-label study of EV in combination with pembrolizumab versus an active comparator-cCRT in adult participants with MIBC who are ineligible for or have elected not to undergo cystectomy. The study is open-label, and the investigators, participants, and sponsor will be aware of the study intervention assignment. The study intervention assignment is by randomization (1:1).
Primary Purpose
Treatment
Masking
None (Open Label)
Masking Description
Open-label

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A 		Enfortumab vedotin + pembrolizumab (EV + P)
  • Drug: Enfortumab vedotin
    Enfortumab vedotin administered as an IV infusion on Days 1 and 8 of every 3-week cycle up to cycle 9.
    Other names:
    • • Padcev
    • • ASG-22CE
    • • ASG-22Me
  • Drug: Pembrolizumab
    IV infusion on Day 1 of every 3-week cycle up to cycle 17.
    Other names:
    • Keytruda
Active Comparator
Arm B 		Concurrent Chemoradiotherapy (cCRT)
  • Radiation: Conventional Radiotherapy
    64 Gy in 32 fractions over 6.5 weeks administered to the participant's bladder only or the bladder and prophylactically to pelvic nodes.
  • Radiation: Hypofractionated Radiotherapy
    55 Gy in 20 fractions over 4 weeks administered to the participant's bladder only.
  • Drug: Cisplatin
    40 mg of cisplatin per meter squared of body surface area, administered once weekly via IV infusion during radiation OR 20 mg of cisplatin per meter squared of body surface area per day on Days 1 and 2 weekly via IV infusion during radiation.
  • Drug: Fluorouracil
    500 mg per meter squared of body surface area per day on Days 1-5 (week 1) and Days 22 26 (week 3) administered as continuous IV infusion during radiation in combination with mitomycin C.
    Other names:
    • • 5-Fluorouracil
    • • 5-FU
  • Drug: Mitomycin C
    12 mg per meter squared of body surface area administered as an IV bolus on Day 1 during radiation in combination with fluorouracil.
    Other names:
    • • MMC
  • Drug: Gemcitabine
    100 mg per meter squared of body surface area administered once weekly via IV infusion during radiation OR 27 mg per meter squared of body surface area administered twice weekly via IV infusion during radiation

Recruiting Locations

Texas Oncology
Austin, Texas 78705

More Details

Status
Recruiting
Sponsor
Astellas Pharma Global Development, Inc.

Study Contact

Pfizer CT.gov Call Center
1-800-718-1021
ClinicalTrials.gov_Inquiries@pfizer.com

Detailed Description

This study is being conducted to evaluate the combination of enfortumab vedotin + pembrolizumab versus standard of care concurrent chemoradiotherapy, in subjects with previously untreated muscle invasive bladder cancer. Enfortumab vedotin may be administered for up to 9 cycles or a protocol defined reason for study discontinuation occurs, whichever is first. Pembrolizumab may be administered for a maximum of 17 cycles (3-week cycles) or a protocol-defined reason for study discontinuation occurs, whichever is first. Concurrent chemoradiotherapy may be administered for a maximum of 6.5 weeks.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.