A Phase 3, Randomized, Double-blind, Placebo-controlled Clinical Trial to Study the Efficacy and Safety of Pembrolizumab in Combination with Chemoradiotherapy versus CRT Alone in Participants with Muscle-invasive Bladder Cancer (MK3475-992/KEYNOTE-992)

General Information Age Group Adults Status Recruiting Protocol Number NCT04241185 Background Information This study is being done to see if pembrolizumab and CRT helps or controls disease. This study will test to see if pembrolizumab and CRT helps participants have a better quality of life compared to CRT alone. The researchers want to confirm the right dose levels of Pembrolizumab and find out what effects (good and bad) Penbrolizumab has on bladder cancer. Pembrolizumab (MK-3475), also known as KEYTRUDA®, has been approved by certain health authorities, such as the U.S. Food and Drug Administration (FDA), for patients with certain types of bladder cancer. However, it has not been approved for MIBC bladder cancer. Getting pembrolizumab in combination with CRT for muscle-invasive bladder cancer (MIBC) is considered experimental. "Experimental" means that the combination of drug plus CRT is currently being tested for this type of cancer. The combination is not approved by the U.S. FDA to treat this specific type of cancer. Principal Investigator Inova Schar Cancer InstituteA department of Inova Fairfax Hospital 8081 Innovation Park Dr. Fairfax, VA 22031 Eligibility Information 18 years of age or older Has a histologically confirmed initial diagnosis of MIBC with predominant urothelial histology (histology and presence of muscle invasion to be confirmed by BICR) obtained via a diagnostic or maximal TURBT performed within 90 days before enrollment Note: Participants with mixed histology are eligible provided the urothelial component is ≥50%. Has planned and is eligible to receive CRT and one of the protocol-specified radiosensitizing chemotherapy regimens. 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 CRT treatment: Refrain from donating sperm PLUS either: 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 (vasectomized or secondary to medical cause [Appendix 5]) as detailed below: Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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 WOCBP OR 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) Agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention. Abstains from breastfeeding during the study intervention period and for at least 120 days (5 half-lives) after study intervention Ineligibility Information Pregnant or breastfeeding Presence of diffuse CIS (multiple foci [4 or greater] of CIS) throughout the bladder. Presence of UC at any site outside of the urinary bladder in the previous 2 years except for Ta/T1/CIS of the upper tract if the patient has undergone a complete nephroureterectomy. Presence of any small cell or neuroendocrine component in the tumor tissue sample. A known additional malignancy that is progressing or has required active therapy within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer or other carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) who have undergone potentially curative therapy are not excluded. Participants with low-risk prostate cancer (T1-T2a, Gleason score ≤6, and PSA <10 ng/mL) either treated with definitive intent any time before screening or untreated in active surveillance are not excluded. Presence of bilateral hydronephrosis during the Screening period. Note: Participants with unilateral hydronephrosis or with a temporary ureteral stent are eligible if their measured or calculated GFR per the institutional standard permits. Limited bladder function with frequency of small amounts of urine (< 30 mL), urinary incontinence, or requires self-catheterization or a permanent indwelling catheter. Received prior pelvic/local radiation therapy or any antineoplastic treatment for MIBC. Note: Prior treatment for NMIBC with intravesical instillation therapy such as BCG or intravesical chemotherapy is permitted, but must be completed ≥28 days before randomization. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor A known severe hypersensitivity (≥Grade 3) to the selected chemotherapy regimen 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. 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). An active infection requiring systemic therapy. A known history of HIV infection. A known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. A known history of active tuberculosis (TB; Bacillus tuberculosis). A known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study. An allogenic tissue/solid organ transplant. Additional eligibility in protocol. For additional information, please go to: https://clinicaltrials.gov/ct2/show/NCT04241185 Contact Information Contact Name Adeeba Ali Contact Phone 571-472-0616 Contact Email Send Email