AN OPEN LABEL, SINGLE ARM, MULTICENTER, SAFETY STUDY OF ATEZOLIZUMAB IN LOCALLY ADVANCED OR METASTATIC UROTHELIAL OR NON-UROTHELIAL CARCINOMA OF THE URINARY TRACT

Phase 3

Completed

• Conditions: urotheel en non-urotheel kanker van de urinewegen; cancer; Urothelial and non-urothelial cancer

• Registration Number: NL-OMON50098
• Lead Sponsor: Roche Nederland B.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

- Age > 18 years;- Histologically documented locally advanced (tumor (T) 4b, any node (N); or any T, N 2*3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract;- Patients with measurable and non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 are allowed;- Must have received one prior combination chemotherapy regimen (e.g., methotrexate, vinblastine, doxorubicin, and cisplatin [MVAC], gemcitabine and cisplatin [GC], etc.) for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract;- Representative formalin-fixed paraffin-embedded (FFPE) tumor specimen block available for submission;- Eastern cooperative oncology group (ECOG) performance status 0, 1 or 2;- Life expectancy ><= 12 weeks;- Adequate hematologic and end-organ function, defined by the following laboratory results obtained within 2 weeks prior to the first study treatment;- Patients with treated, asymptomatic central nervous system (CNS) metastases are eligible (Note: Patients on stable doses of anticonvulsants or on prednisone doses [or dose equivalents] of <<= 20 milligram/day are allowed);- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab

Exclusion Criteria

- Treatment with more than three prior lines of systemic therapy for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract;- Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to study treatment initiation;- Treatment with chemotherapy within 2 weeks prior to study treatment initiation;- Treatment with radiotherapy ongoing at the time of study entry (for CNS-directed radiotherapy);- Pregnant or lactating, or intending to become pregnant during the study;- Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome);- Significant cardiovascular disease, such as New York Heart Association cardiac disease >= Class III, myocardial infarction within 3 months, unstable arrhythmias, or unstable angina;- Significant renal disorder requiring dialysis or indication for renal transplant;- Signs or symptoms of severe infection within 2 weeks prior to initiation of study treatment, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia;- Major surgical procedure within 4 weeks prior to study treatment initiation or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis;- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins;- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation;- History of autoimmune disease are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks;- Prior allogeneic stem cell or solid organ transplantation;- History of idiopathic pulmonary fibrosis (including pneumonitis, drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan;- Patients with active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C;- Active tuberculosis;- Administration of a live, attenuated vaccine within 4 weeks prior to study treatment initiation;- Prior treatment with cluster of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, including anti* cytotoxic T lymphocyte-associated (CTLA)-4, anti* programmed cell death protein 1 (PD-1), and anti* programmed death-ligand 1 (PD-L1) therapeutic antibodies;- Treatment with systemic immunostimulatory agents (including, but not limited to, interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment;- Specifically for patients without autoimmune disease, treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to study treatment initiation or anticipated requirement for systemic immunosuppressive medications during the study treatment period. Note: For patients with autoimmune disease, immunosuppressive medications are permitted if the patient has controlled autoimmune disease and stable treatment (i.e., same treatment, same dose) for the previous

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective of this study is to evaluate the safety of atezolizumab<br /><br>based on the following endpoints:<br /><br><br /><br>* Nature, severity, duration, frequency and timing of adverse events (AEs)<br /><br>* Changes in vital signs, physical findings, and clinical laboratory results<br /><br>during and following atezolizumab administration<br /><br><br /><br>Safety assessments will consist of monitoring and recording adverse events,<br /><br>including SAEs and adverse events of special interest, performing<br /><br>protocol-specified safety laboratory assessments, measuring protocol-specified<br /><br>vital signs, and conducting other protocol-specified tests that are deemed<br /><br>critical to the safety evaluation of the study.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary objectives of the study include evaluation of the efficacy of<br /><br>atezolizumab based on the following disease response endpoints:<br /><br>* Overall survival (OS)<br /><br>* Progression-free survival (PFS<br /><br>* Overall response rate (ORR), defined as the proportion of patients with a<br /><br>best overall response of either complete response (CR) or partial response<br /><br>(PR).<br /><br>* Disease control rate (DCR)<br /><br>* Duration of response (DoR)<br /><br>* Evaluation of efficacy of atezolizumab according to the following<br /><br>patient-reported outcomes</p><br>