A Study of Atezolizumab in Combination With Gemcitabine/Carboplatin Versus Gemcitabine/Carboplatin plus placebo in Patients With Untreated Urothelial Carcinoma who are Ineligible for Cisplatin-Based Therapy

Phase 1

• Conditions: rothelial Carcinoma, locally advanced or metastatic; MedDRA version: 19.0Level: LLTClassification code 10064467Term: Urothelial carcinomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000250-35-ES
• Lead Sponsor: Roche Farma, S.A., que representa en España a F. Hoffmann-La Roche Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-06-16
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 435

Inclusion Criteria

- Age >= 18 years
- 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
- Ineligible for cisplatin-based chemotherapy
- 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 or gemcitabine or for 90 days after the last dose of atezolizumab
- 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 or gemcitabine or for 90 days after the last dose of atezolizumab
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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 265

Exclusion Criteria

- 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 < 2.5 gram per deciliter
Exclusion Criteria Related to Atezolizumab:
- 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
- Known hypersensitivity to gemcitabine
- History of severe allergic reactions to cisplatin or other platinum-containing compounds
- Severe bone marrow depression or significant bleeding

Study & Design

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