Study of MEDI4736 (Durvalumab) With or Without Tremelimumab Versus Standard of Care Chemotherapy in Urothelial Cancer
Condition: Urothelial Cancer
Intervention: MEDI4736 (Durvalumab); Tremelimumab; Cisplatin; Carboplatin; Gemcitabine
Intervention description: IV infusion; IV infusion; IV infusion; IV infusion; IV infusion
Intervention MeSH terms: Carboplatin; Gemcitabine; Durvalumab; Tremelimumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1126.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Urothelial Cancer; Phase III

Summary:

      A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line
      MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination with Tremelimumab
      Versus Standard of Care Chemotherapy in Patients with Stage IV Urothelial Cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with histologically or cytologically documented, unresectable, Stage IV
             transitional cell carcinoma of the urothelium who have not been previously treated
             with first-line chemotherapy.

          -  Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin
             ineligibility is defined as meeting 1 of the following criteria: • Creatinine
             clearance (calculated or measured) <60 mL/min calculated by Cockcroft-Gault equation
             (using actual body weight) or by measured 24-hour urine collection for determination •
             Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing
             loss • CTCAE Grade ≥2 peripheral neuropathy • New York Heart Association ≥Class III
             heart failure.

          -  Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference
             laboratory, must be known prior to randomization.

        Exclusion Criteria:

          -  Prior exposure to immune-mediated therapy, including but not limited to, other anti
             cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or
             anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local
             intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days
             prior to the initiation of study treatment.

          -  History of allogenic organ transplantation that requires use of immunosuppressive
             agents.

          -  Active or prior documented autoimmune or inflammatory disorders. The following are
             exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with
             hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any
             chronic skin condition that does not require systemic therapy • Patients without
             active disease in the last 3 years may be included but only after consultation with
             AstraZeneca • Patients with celiac disease controlled by diet alone may be included
             but only after consultation with AstraZeneca.

          -  Brain metastases or spinal cord compression unless the patient's condition is stable
             and off steroids for at least 14 days prior to the start of study treatment. Patients
             with suspected or known brain metastases at screening should have an MRI
             (preferred)/CT, preferably with IV contrast to access baseline disease status.

          -  Active infection including tuberculosis, hepatitis B, hepatitis C, or human
             immunodeficiency virus (HIV).

          -  Current or prior use of immunosuppressive medication within 14 days before the first
             dose of investigational product (IP). The following are exceptions to this criterion:
             • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra
             articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10
             mg/day of prednisone or its equivalent • Steroids as premedication for
             hypersensitivity reactions (eg, CT scan premedication).

          -  Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note:
             Patients, if enrolled, should not receive live vaccine during the study and up to 30
             days after the last dose of IP.