Study of Durvalumab Given with Chemotherapy, Durvalumab in Combination with Tremelimumab Given with Chemotherapy, or Chemotherapy in Patients with Advanced Urothelial Bladder Cancer

Phase 1

Conditions: Patients with Unresectable Locally Advanced or Metastatic Urothelial Cancer
MedDRA version: 20.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-001883-48-HU

Lead Sponsor: Astrazeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1434

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.
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 574
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 860

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

Name	Time	Method
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 <br><br>-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);Timepoint(s) of evaluation of this end point: Assessments for overall survival will be made periodically until the end of study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Progression Free Survival (PFS) <br>- Overall Survival (OS)<br>- Alive and Progression Free Patients at 12 Months (APF12)<br>- Overall Response Rate (ORR) <br>- Disease Control Rate (DCR)<br>- Duration of Response (DoR)<br>- Time from Randomization to Second Progression PFS (PFS2)<br>- Safety<br>- Disease related symptoms;Timepoint(s) of evaluation of this end point: Assessments will be made periodically until the end of study.

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