A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination with Standard of Care Chemotherapy and Durvalumab in Combination with Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer
Clinical Trial Information
Trial Contact: Walton, Sherri; Manchola-Orozco, Carolina; Cevallos, Claudia
IRB No: WIRB20181990
Protocol Abbrev: TRIO NILE
Principal Investigator: Daniel Ari Landau, MD
Phase: Drug: Phase III
Age Group: Adult
Secondary Protocol No: D933SC00001
Treatment: 3 Arms: -Durvalumab in Combination with SoC Chemotherapy -Durvalumab in Combination with Tremelimumab+SoC Chemotherapy -SoC Chemotherapy
Therapies Involved: Oncology: 1st line
ClinicalTrials.gov ID: NCT03682068
To determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).
Key Inclusion Criteria:
• Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
• Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
• At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
• World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
• Adequate organ and marrow function as defined in the protocol
• Life expectancy ≥12 weeks in the opinion of the investigator
• Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
Key Exclusion Criteria:
• Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
• No severe concomitant condition that requires immunosuppression medication
• Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Patients who may be eligible for or are being considered for radical resection during the course of the study.
• Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients