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

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2016-000250-35-SI
• Date of registration: 05/07/2016
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche Ltd
• Public title: A Study of Atezolizumab as Monotherapy And in Combination With Platinum-Based Chemotherapy compared to Platinum-Based Chemoteraphy in Patients With Untreated Urothelial Carcinoma
• Scientific title: A Phase III, multicenter, randomized, placebo-controlled study of atezolizumab (anti-PD-L1 antibody) as monotherapy and in combination with platinum-based chemotherapy in patients with untreated locally advanced or metastatic urothelial carcinoma
• Date of first enrolment: 03/08/2016
• Target sample size: 1200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000250-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: a third treatment arm was added (open-label atezolizumab monotherapy) If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Brazil, Chile, China, Czech Republic, Czechia, Estonia, Finland, Greece, Hong Kong, Italy, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Slovenia, South Africa, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd

Key inclusion & exclusion criteria

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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Urothelial Carcinoma, locally advanced or metastatic
MedDRA version: 20.0 Level: LLT Classification code 10064467 Term: Urothelial carcinoma System Organ Class: 100000004864

Intervention(s)

Product Name: atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Carboplatin-GRY®
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: carboplatin
Other descriptive name: CARBOPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Gitrabin
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: GEMCITABINE
CAS Number: 95058-81-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 38-

Trade Name: Cisplatin Hospira
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Cisplatin Teva
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: cisplatin
Other descriptive name: CISPLATIN
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1-

Trade Name: Tecentriq
Product Name: atezolizumab
Product Code: RO5541267
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other descriptive name: MPDL3280A
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 60-

Trade Name: Cisplatin Teva
Pharmaceutical Form: Concentrate

Primary Outcome(s)

Secondary Objective: • To evaluate efficacy of Atezo given as either monotherapy or in combination with platinum-based chemotherapy vs. placebo in combination with platinum-based chemotherapy based on objective response rate, duration of response, independent review facility-PFS, OS rate, PFS rate, time to deterioration in global health status and in physical function as measured by Quality-of-Life Questionnaire Core 30
• Investigator-assessed PFS for Atezo monotherapy vs. placebo plus platinum-based chemotherapy
• To evaluate safety and tolerability of Atezo given as either monotherapy or in combination with platinum-based chemotherapy vs. placebo plus platinum-based chemotherapy
• To characterize pharmacokinetics of Atezo when administered as monotherapy or in combination with platinum-based chemotherapy in patients who are treatment-naive

Primary end point(s): 1. PFS as assessed by the investigator using RECIST v1.1 (Atezo plus platinum-based chemotherapy vs. placebo plus platinum-based chemotherapy arms only)
2. OS (Atezo plus platinum-based chemotherapy vs. placebo plus platinum-based chemotherapy arms only)
3. OS (Atezo monotherapy vs. placebo plus platinum-based chemotherapy)

Timepoint(s) of evaluation of this end point: 1-3. Up to 44 months

Main Objective: • To evaluate efficacy of atezolizumab (Atez) plus platinum-based chemotherapy vs. placebo plus platinum-based chemotherapy based on progression-free survival (PFS) and overall survival (OS)
• To evaluate efficacy of Atez monotherapy compared vs. placebo plus platinum-based chemotherapy on the basis of OS

Secondary Outcome(s)

Secondary end point(s): 1. Objective Response Rate (ORR)
2. Duration of Response (DOR)
3. Independent Review Facility - PFS
4. Investigator assessed PFS using RECIST v1.1 (Atez monotherapy vs. placebo plus platinum-based chemotherapy)
5. OS rate
6. PFS rate
7. Time to deterioration in global health status and physical function as measured by the EORTC QLQ-C30
Safety
8. Incidence, nature and severity of adverse events
9. Changes in vital signs and clinical laboratory results
Pharmacokinetic
10. Maximum and minimum serum concentration of Atez
Immunogenicity
11. Incidence of anti-therapeutic antibodies (ATAs) during the study relative to the prevalence of ATAs at baseline

Timepoint(s) of evaluation of this end point: 1-4. When the required number of events has been observed for the final OS analysis in the main study’s ITT population
5-6. 1 year
7-9. When the required number of events has been observed for the final OS analysis in the main study’s ITT population
10-11. Pre-dose Cycle (C) 1 Day (D) 1, D1 of C2, C3, C4, and C8, at treatment discontinuation, 120 days (+/- 30 days) after last dose of Atezo

Secondary ID(s)

WO30070

2016-000250-35-ES

Source(s) of Monetary Support

F. Hoffmann-La Roche Ltd

Ethics review

Status: Approved
Approval date: 27/07/2016
Contact:

Results

• Results available: Yes
• Date Posted: 08/09/2023
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-000250-35/results