Brief Title
Study of Atezolizumab as Monotherapy and in Combination With Platinum-Based Chemotherapy in Participants With Untreated Locally Advanced or Metastatic Urothelial Carcinoma
Official 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
Brief Summary
A Phase III, randomised study of atezolizumab alone and in combination with chemotherapy
versus chemotherapy alone in participants with untreated advanced urothelial cancer.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Progression-Free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Participants Treated with Atezolizumab Combination Therapy Compared With Placebo Arm
Secondary Outcome
Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) Assessed by Investigator Using RECIST v1.1
Condition
Urothelial Carcinoma
Intervention
Atezolizumab
Study Arms / Comparison Groups
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin
Description: Participants will receive blinded atezolizumab in combination with open-label platinum-based chemotherapy (gemcitabine with either cisplatin or carboplatin).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
1214
Start Date
June 30, 2016
Completion Date
June 30, 2023
Primary Completion Date
June 30, 2023
Eligibility Criteria
Inclusion Criteria
- Considered to be eligible to receive platinum-based chemotherapy, in the
investigator's judgment
- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
() 12
months between the last treatment administration and the date of recurrence is
required in order to be considered treatment naive in the metastatic setting
- Prior local intravesical chemotherapy or immunotherapy is allowed if completed at
least 4 weeks prior to the initiation of study treatment
- Measurable disease, as defined by 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
atezolizumab
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures and agreement to refrain from donating sperm
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 enrolment
- Active or untreated CNS metastases as determined by computed tomography (CT) or
magnetic resonance imaging evaluation during screening and prior radiographic
assessments
- Participants with treated asymptomatic central nervous system (CNS) metastases are
eligible, provided they meet all of the following criteria: * Evaluable or measurable
disease outside the CNS * No metastases to midbrain, pons, medulla, or within 10 mm of
the optic apparatus (optic nerves and chiasm) * No history of intracranial or spinal
cord hemorrhage * No ongoing requirement for corticosteroid as therapy for CNS
disease; anti-convulsants at a stable dose are allowed * No evidence of significant
vasogenic edema * No stereotactic radiation, whole-brain radiation or neurosurgical
resection within 4 weeks prior to Cycle 1, Day 1 * Radiographic demonstration of
interim stability (i.e., no progression) between the completion of CNS-directed
therapy and the screening radiographic study * Screening CNS radiographic study >/=4
weeks since completion of radiotherapy or surgical resection and >/=2 weeks since
discontinuation of corticosteroids
- Prior treatment with CD137 agonists, anti-CTLA-4, anti-programmed death-1 (PD-1), or
anti-PD-L1 therapeutic antibody or pathway-targeting agents
- Treatment with systemic corticosteroids or other systemic immunosuppressive
medications (including but not limited to prednisone, dexamethasone, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents)
within 2 weeks prior to Cycle 1, Day 1 or anticipated requirement for systemic
immunosuppressive medications during the study
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
- Uncontrolled tumour-related pain or hypercalcemia
- Significant cardiovascular disease including known left ventricular ejection fraction
(LVEF) <40%
- Severe infections within 4 weeks before randomization or therapeutic oral or IV
antibiotics within 2 weeks before randomization
- Major surgical procedure within 4 weeks prior to randomization or anticipation of need
for a major surgical procedure during the course of the study other than for diagnosis
- Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
- Life expectancy of <12 weeks
- Pregnant or lactating, or intending to become pregnant during the study
- Serum albumin <25 gram per liter (g/L)
- 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
- Participants with 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 CT scan
- Positive test for human immunodeficiency virus (HIV)
- Active hepatitis B or hepatitis C
- Active tuberculosis
- Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Clinical Trials, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT02807636
Organization ID
WO30070
Secondary IDs
2016-000250-35
Responsible Party
Sponsor
Study Sponsor
Hoffmann-La Roche
Study Sponsor
Clinical Trials, Study Director, Hoffmann-La Roche
Verification Date
January 2023