Titre A Phase 3 Randomized Study of Cystectomy Plus Perioperative Pembrolizumab Versus Cystectomy Alone in Cisplatin-ineligible Participants With Muscle-invasive Bladder Cancer
Protocole ID MK-3475-905 (KEYNOTE-905)
ClinicalTrials.gov ID NCT03924895
Type(s) de cancer Vessie/urothélial
Phase Phase III
Type étude Traitement
Médicament Pembrolizumab
Institution CIUSSS DE L'EST-DE-L'ILE-DE-MONTREAL
   PAV. MAISONNEUVE/PAV. MARCEL-LAMOUREUX
      5415 boul. de l'Assomption, Montréal, QC, H1T2M4
Ville Montréal
Investigateur(trice) principal(e) Dr Nawar Hanna
Coordonnateur(trice) Audrey Lamoureux
 514-252-3400 poste 6258
Statut Fermé
Critètes d'éligibilité
  • Histologically confirmed diagnosis of muscle invasive bladder cancer (T2-T4aN0M0) with predominant (≥50%) urothelial histology. Participants with mixed histology are eligible provided the urothelial component is ≥50%. Urothelial carcinomas not originating from the bladder are not eligible. Participants whose tumors contain any neuroendocrine component are not eligible.
  • Clinically non-metastatic bladder cancer determined by imaging
  • Eligible for radical cystectomy (RC) + pelvic lymph node dissection (PLND ), and agreement to undergo curative intent standard RC + PLND (including prostatectomy if applicable)
  • Ineligible for treatment with cisplatin, as defined by meeting at least one of the following criteria:
  • Impaired renal function with measured or calculated CrCl 30 to 59 mL/min
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 2
  • Common Terminology Criteria for Adverse Events (CTCAE) v.4 Grade ≥2 audiometric hearing loss
  • CTCAE v.4 Grade ≥2 peripheral neuropathy
  • New York Heart Association (NYHA) Class III heart failure
  • Transurethral resection (TUR) of a bladder tumor that is submitted and adequate for evaluation of histology, muscle invasion and PD-L1 status
  • ECOG performance status of 0, 1, or 2
  • Adequate organ function
Critètes d'exclusion
  • Known additional non-urothelial malignancy that is progressing or has required active treatment ≤3 years of study randomization, with certain exceptions
  • Received any prior systemic anti-neoplastic treatment for muscle-invasive bladder cancer (MIBC)
  • Received prior therapy with a anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-programmed cell death 1 ligand 2 (PD-L2), or with an agent directed to another stimulatory or co-inhibitory T-cell receptor
  • Received prior systemic anti-cancer therapy including investigational agents within 3 years prior to randomization
  • Received any prior radiotherapy to the bladder
  • Received a live vaccine within 30 days prior to the first dose of study drug
  • Current participation in or participation in a study of an investigational agent or use of an investigational device within 4 weeks prior to the first dose of study intervention
  • Diagnosis of immunodeficiency or receipt of chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
  • Hypersensitivity to monoclonal antibodies (including pembrolizumab) and/or any of their excipients
  • Active autoimmune disease that has required systemic therapy in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic therapy and is allowed.
  • History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
  • Active infection requiring systemic therapy