Study of First Line MEDI4736 with or without Tremelimumab versus Standard of Care Chemotherapy in Advanced Unresectable Urothelial Bladder Cancer

Phase 1

Conditions: Adult patients (age =18 years) with histologically or cytologically documented transitional cell carcinoma (transitional cell and mixed transitional/non transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra), unresectable Stage IV (ie, =T4bN0M0 for bladder), and who are chemotherapy-naïve.
MedDRA version: 21.0Level: LLTClassification code 10022880Term: Invasive bladder cancer stage IVSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2015-001633-24-BE

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 1005

Inclusion Criteria

1, 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.
2, Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria: • Creatinine clearance <60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection • 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.
3, Tumor PD-L1 status, with IHC assay confirmed by a reference laboratory, must be known prior to randomization.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 700
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 305

Exclusion Criteria

1, Prior exposure to immune-mediated therapy, including but not limited to, other anti-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. 2, History of allogenic organ transplantation that requires use of immunosuppressive agents. 3,
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. 4, 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. 5, Active infection including
tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus
(HIV). 6, 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). 7, 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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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