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Brief Title: Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Muscle-invasive Bladder Cancer (MIBC) (MK-3475-992/KEYNOTE-992)

A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Chemoradiotherapy (CRT) Versus CRT Alone in Participants With Muscle-invasive Bladder Cancer (MIBC) (KEYNOTE-992)

INTRODUCTION

  • Org Study ID: 3475-992
  • Secondary ID: N/A
  • NCT ID: NCT04241185
  • Sponsor: Merck Sharp & Dohme LLC

BRIEF SUMMARY

This study is designed to assess the antitumor efficacy and safety of pembrolizumab in combination with chemoradiotherapy (CRT) versus CRT alone in participants with muscle-invasive bladder cancer (MIBC). The primary hypothesis is that pembrolizumab + chemoradiotherapy is superior to placebo + chemoradiotherapy with respect to bladder intact event-free survival.

  • Overall Status
    Recruiting
  • Start Date
    May 19, 2020
  • Phase
    Phase 3
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

  • Urinary Bladder Neoplasms

ELIGIBILITY

Inclusion Criteria:
* Has a histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology

- * Has clinically nonmetastatic bladder cancer (N0M0)

- * Has planned and is eligible to receive chemoradiotherapy (CRT) and one of the protocol-specified radiosensitizing chemotherapy regimens

- * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- * Demonstrates adequate organ function

- * Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of CRT treatment:
* Refrain from donating sperm

- * Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic

- * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a woman of childbearing potential (WOCBP)

- * Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 180 days the time needed to eliminate each study intervention after the last dose of study intervention; and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: MK-3475 - 120 days and CRT - 180 days
Exclusion Criteria:
* Has the presence of diffuse carcinoma in situ (CIS) (multiple foci of CIS) throughout the bladder

- * Has the presence of urothelial carcinoma (UC) at any site outside of the urinary bladder in the previous 2 years except for Ta stage/T1 stage/CIS of the upper tract if the participant has undergone a complete nephroureterectomy

- * Has a known additional malignancy that is progressing or has required active therapy within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ that has undergone potentially curative therapy

- * Has the presence of bilateral hydronephrosis

- * Has limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter - * Has received prior pelvic/local radiation therapy or any antineoplastic treatment for muscle-invasive bladder cancer (MIBC). Treatment for non-muscle invasive bladder cancer (NMIBC) with intravesical instillation therapy that was completed ≥28 days prior to randomization is allowed. Prior systemic treatment of NMIBC is not permitted. - * Received prior therapy with an anti-PD-1 (programmed cell death protein 1), anti-PD-L1 (programmed death-ligand 1), or anti-PD-L2 (programmed cell death 1 ligand 2), or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., CTLA-4 [cytotoxic T-lymphocyte-associated protein 4], OX 40, or CD137 [cluster of differentiation 137]) - * Has received a live vaccine within 30 days before the first dose of study medication - * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study medication - * Has known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen, and/or any of their excipients and excipients of pembrolizumab - * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study medication - * Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed - * Has a history of non-infectious pneumonitis that required steroids or has current pneumonitis - * Has an active infection requiring systemic therapy - * Has a known history of human immunodeficiency virus (HIV) infection - * Has a known history of hepatitis B or known active hepatitis C virus infection - * Has a known history of active tuberculosis (TB; Bacillus tuberculosis) - * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study - * Has had an allogenic tissue/solid organ transplant

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Medical Director

Role: Study Director

Affiliation: Merck Sharp & Dohme LLC

Overall Contact

Name: Toll Free Number

Phone: 1-888-577-8839

Email: Trialsites@merck.com

LOCATION

Facility Status Contact
Facility: Washington Cancer Institute at MedStar Washington Hospital Center ( Site 0041)
Washington, District of Columbia 20010
United States
Status: Recruiting Contact: Contact
Study Coordinator
202-877-9386

Facility: Washington University ( Site 0003)
Saint Louis, Missouri 63110
United States
Status: Recruiting Contact: Contact
Study Coordinator
314-747-4328

Facility: Summit Medical Group Cancer Center ( Site 6008)
Florham Park, New Jersey 07932
United States
Status: Recruiting Contact: Contact
Study Coordinator
855-413-2220

Facility: John Theurer Cancer Center at Hackensack University Medical Center ( Site 0005)
Hackensack, New Jersey 07601
United States
Status: Recruiting Contact: Contact
Study Coordinator
551-996-1379

Facility: New York Oncology Hematology P.C ( Site 0024)
Albany, New York 12206
United States
Status: Recruiting Contact: Contact
Study Coordinator
518-489-3612

Facility: Roswell Park Cancer Institute ( Site 6009)
Buffalo, New York 14203
United States
Status: Recruiting Contact: Contact
Study Coordinator
716-845-4922

Facility: Winthrop University Hospital ( Site 0069)
Mineola, New York 11501
United States
Status: Recruiting Contact: Contact
Study Coordinator
516-289-3772

Facility: New York University Perlmutter Cancer Center ( Site 0001)
New York, New York 10016
United States
Status: Recruiting Contact: Contact
Study Coordinator
212-731-6455

Facility: Cleveland Clinic ( Site 0062)
Cleveland, Ohio 44195
United States
Status: Recruiting Contact: Contact
Study Coordinator
866-223-8100

Facility: MidLantic urology ( Site 0070)
Bala-Cynwyd, Pennsylvania 19004
United States
Status: Recruiting Contact: Contact
Study Coordinator
610-667-0458

Facility: Carolina Urologic Research Center ( Site 0002)
Myrtle Beach, South Carolina 29572
United States
Status: Recruiting Contact: Contact
Study Coordinator
843-449-1010 ext. 257

Facility: Urology San Antonio Research ( Site 6010)
San Antonio, Texas 78229
United States
Status: Recruiting Contact: Contact
Study Coordinator
832-472-5482

Facility: West Virginia University - Charleston Area Medical Center ( Site 6003)
Charleston, West Virginia 25304
United States
Status: Recruiting Contact: Contact
Study Coordinator
304-388-5432

Facility: Froedtert and Medical College of Wisconsin ( Site 0022)
Milwaukee, Wisconsin 53226
United States
Status: Recruiting Contact: Contact
Study Coordinator
414-805-8900