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A Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide in Participants With Metastatic Castration-Resistant Prostrate Cancer (mCRPC) After Failure of an Androgen Synthesis Inhibitor And Failure of, Ineligibility For, or Refusal of a Taxane Regimen (IMbassador250)

This study is currently recruiting participants.
Verified September 2017 by Hoffmann-La Roche
Sponsor:
ClinicalTrials.gov Identifier:
NCT03016312
First Posted: January 10, 2017
Last Update Posted: September 15, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Hoffmann-La Roche
  Purpose
This Phase III, multicenter, randomized, open-label study will evaluate the safety and efficacy of atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) in combination with enzalutamide compared with enzalutamide alone in participants with mCRPC after failure of an androgen synthesis inhibitor (e.g., abiraterone) and failure of, ineligibility for, or refusal of a taxane regimen. Participants will be randomized to one of the two treatment arms (atezolizumab in combination with enzalutamide, and enzalutamide alone) in a 1:1 ratio (experimental to control arm) in global randomized phase. Participants will receive treatment until investigator-assessed confirmed radiographic disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria or unacceptable toxicity.

Condition Intervention Phase
Prostatic Neoplasms, Castration-Resistant Drug: Atezolizumab Drug: Enzalutamide Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Enzalutamide Versus Enzalutamide Alone in Patients With Metastatic Castration-Resistant Prostate Cancer After Failure of an Androgen Synthesis Inhibitor and Failure of, Ineligibility for, or Refusal of a Taxane Regimen

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Overall surivival (OS) [ Time Frame: Baseline until death from any cause (up to approximately 42 months) ]

Secondary Outcome Measures:
  • Percentage of Participants who Survived at Month 12 and 24 [ Time Frame: Months 12, 24 ]
  • Time to Cancer-Related Pain Progression, as Assessed Using Modified Brief Pain Inventory (BPI) [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
  • Time to First Symptomatic Skeletal Event (SSE) [ Time Frame: Baseline up to end of study (up to approximately 42 months) ]
  • Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
  • Percentage of Participants Who are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria [ Time Frame: Months 6, 12 ]
  • Immune-Modified rPFS, as Assessed by the Investigator as per PCWG3 Criteria and Immune-Modified Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
  • Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
  • Time to PSA Progression, Assessed as per PCWG3 Criteria [ Time Frame: Baseline until disease progression (up to approximately 42 months) ]
  • Percentage of Participant With Objective Response, as Determined by the Investigator Through use of PCWG3 Criteria [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
  • Percentage of Participant With Objective Response, as Determined by the Investigator Through use of Immune-Modified RECIST [ Time Frame: Baseline until disease progression or death from any cause (up to approximately 42 months) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to end of study (up to approximately 42 month ]
  • Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (0 hour[hr]) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5 hr post-infusion (infusion duration: 60 minutes [min]) on Day 1 Cycle 1; treatment discontinuation visit, 120 days after last dose (up to approximately 42 months) ]
  • Plasma Concentration of Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
  • Plasma Concentration of N-Desmethyl Enzalutamide [ Time Frame: Predose (0 hr) and 1 hr postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (within 1 hr) on Day 1 Cycle 8 ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: Predose (0 hr) on Day 1 Cycles 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of atezolizumab; up to 42 months ]
  • Time to Initiation or Increased Opiate Analgesic Use [ Time Frame: Baseline up to end of study (up to approximately 42 months) ]

Estimated Enrollment: 730
Actual Study Start Date: January 11, 2017
Estimated Study Completion Date: July 9, 2022
Estimated Primary Completion Date: November 11, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atezolizumab + Enzalutamide
Participants will receive atezolizumab along with enzalutamide until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Drug: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.
Other Name: Tecentriq®
Drug: Enzalutamide
Enzalutamide capsules will be administered orally at a dose of 160 mg daily.
Other Name: Xtandi®
Active Comparator: Enzalutamide
Participants will receive enzalutamide alone until investigator-assessed confirmed radiographic disease progression per PCWG3 criteria or unacceptable toxicity (up to approximately 42 months).
Drug: Enzalutamide
Enzalutamide capsules will be administered orally at a dose of 160 mg daily.
Other Name: Xtandi®

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy greater than or equal to (>/=) 3 months
  • Histologically confirmed adenocarcinoma of the prostate
  • Known castrate-resistant disease with serum testosterone level less than or equal to (</=) 50 nanograms per deciliter (ng/dL) with prior surgical castration or ongoing androgen deprivation for the duration of the study
  • Progressive disease prior to screening by PSA or imaging per PCWG3 criteria during or following the direct prior line of therapy in the setting of medical or surgical castration
  • One prior regimen/line of a taxane-containing regimen for mCRPC or refusal or ineligibility of a taxane-containing regimen
  • Progression on a prior regimen/line of an androgen synthesis inhibitor for prostate cancer
  • Availability of a representative tumor specimen from a site not previously irradiated that is suitable for determination of programmed death-ligand 1 (PD-L1) status via central testing
  • Adequate hematologic and end organ function

Exclusion Criteria:

  • Prior treatment with enzalutamide or any other newer hormonal androgen receptor inhibitor (e.g., apalutamide, ODM-201)
  • Treatment with any approved anti-cancer therapy, including chemotherapy, immunotherapy, radiopharmaceutical or hormonal therapy (with the exception of abiraterone), within 4 weeks prior to initiation of study treatment
  • Treatment with abiraterone within 2 weeks prior to study treatment
  • Structurally unstable bone lesions suggesting impending fracture
  • Known or suspected brain metastasis or active leptomeningeal disease
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
  • Active or history of autoimmune disease or immune deficiency
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Positive human immunodeficiency virus (HIV) test, active tuberculosis, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
  • Prior treatment with cluster of differentiation (CD)137 agonists or immune checkpoint blockade therapies, including anti Cytotoxic T Lymphocyte-Associated 4 (CTLA4), anti-programmed death 1 (PD-1), and anti-PD-L1 therapeutic antibodies
  • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug, whichever is shorter, prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study
  • History of seizure or any condition that may predispose to seizure within 12 months prior to study treatment, including history of unexplained loss of consciousness or transient ischemic attack
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03016312


Contacts
Contact: Reference Study ID Number: CO39385 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 198 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03016312     History of Changes
Other Study ID Numbers: CO39385
2016-003092-22 ( EudraCT Number )
First Submitted: January 9, 2017
First Posted: January 10, 2017
Last Update Posted: September 15, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Antibodies
Antibodies, Monoclonal
Androgens
Atezolizumab
Taxane
Steroid Synthesis Inhibitors
Immunologic Factors
Physiological Effects of Drugs
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists