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A trial to learn how well durvalumab and chemotherapy with or without tremelimumab work in adults with advanced cancer of the bladder or urinary system

Phase 1
Recruiting
Conditions
Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer
MedDRA version: 20.0Level: PTClassification code: 10005003Term: Bladder cancer Class: 100000004864
Therapeutic area: Diseases [C] - Neoplasms [C04]
Registration Number
CTIS2024-510976-19-00
Lead Sponsor
AstraZeneca AB
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Recruiting
Sex
All
Target Recruitment
1274
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.

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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess the efficacy of durvalumab + SoC combination therapy versus SoC in terms of OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression.<br><br>To assess the efficacy of Durvalumab and Tremelimumab + SoC combination therapy versus SoC in terms of OS in patients with unresectable locally advanced or metastatic UC and high PD-L1 expression.;Secondary Objective: To assess the efficacy in patients in different treatment arms, To assess disease-related symptoms, safety, physical functioning, and other health related quality of life in patients in different treatment arms;Primary end point(s): Overall Survival (OS)
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s):Progression Free Survival (PFS) - Overall Survival (OS) - Alive and Progression Free Patients at 12 Months (APF12) - Overall Response Rate (ORR) - Disease Control Rate (DCR) - Duration of Response (DoR) - Time from Randomization to Second Progression PFS (PFS2) - Safety - Disease related symptoms
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