A Study of Atezolizumab as Monotherapy And in Combination With Platinum-Based Chemotherapy compared to Platinum-Based Chemotherapy in Patients With Untreated Urothelial Carcinoma

Phase 1

• Conditions: rothelial Carcinoma, locally advanced or metastatic; MedDRA version: 20.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000250-35-PT
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-16
• Last Update Posted: 21 May 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1213

Inclusion Criteria

- Age >= 18 years
- Considered to be eligible to receive platinum-based chemotherapy, in the investigator’s judgment
- Eastern Cooperative Oncology Group performance status of <= 2
- Histologically documented, locally advanced (T [tumor] 4b, any N [nodes]; or any T, N 2-3) or metastatic urothelial carcinoma (mUC) (M [metastasized] 1, Stage IV)
- Representative formalin-fixed paraffin-embedded tumor specimens in paraffin blocks or at least 15 unstained slides
- No prior chemotherapy for inoperable locally advanced or mUC
- Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Adequate hematologic and end-organ function
- 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 6 months after the last dose of carboplatin, cisplatin, or gemcitabine or for 5 months after the last dose of Atez
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm that together result in a failure rate of < 1% per year during the treatment period and for at least 6 months after the last dose of carboplatin and or gemcitabine, and/or cisplatin

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 468
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 732

Exclusion Criteria

Cancer-Specific Exclusions:
- Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
- Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 28 days prior to enrollment
- Active or untreated central nervous system metastases as determined by computed tomography or magnetic resonance imaging evaluation during screening and prior radiographic assessments
- Leptomeningeal disease
- Uncontrolled hypercalcemia, tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
General Medical Exclusions:
- Life expectancy of < 12 weeks
- Pregnant or lactating, or intending to become pregnant during the study
- Serum albumin < 25 gram per liter
Exclusion Criteria Related to Atez:
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- History of autoimmune disease
- Patients with prior allogeneic stem cell or solid organ transplantation
- History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia or evidence of active pneumonitis
- Significant cardiovascular disease
- Known left ventricular ejection fraction < 40%
- Positive test for HIV
- Active hepatitis B or hepatitis C, tuberculosis
- Severe infections within 4 weeks prior to randomization
- Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
- Prior treatment with Cluster of Differentiation (CD) 137 agonists, anti- cytotoxic T-lymphocyte-associated protein (CTLA)-4, anti- programmed cell death protein (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with systemic immunostimulatory agents, systemic corticosteroids or other systemic immunosuppressive medications
Exclusion Criteria Related to Gemcitabine:
- Known hypersensitivity to gemcitabine
Exclusion Criteria Related to Carboplatin:
- History of severe allergic reactions to cisplatin or other platinum-containing compounds
- Severe bone marrow depression or significant bleeding
Exclusion Criteria Related to Cisplatin:
- Patients with preexisting renal impairment
- Patients with myelosuppresion or hearing impairment
- History of allergic reactions to cisplatin or other platinum-containing compounds

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified