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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)

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ClinicalTrials.gov Identifier: NCT03016312
Recruitment Status : Active, not recruiting
First Posted : January 10, 2017
Last Update Posted : January 14, 2020
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE January 9, 2017
First Posted Date  ICMJE January 10, 2017
Last Update Posted Date January 14, 2020
Actual Study Start Date  ICMJE January 10, 2017
Estimated Primary Completion Date March 21, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2019)
Overall Survival (OS) [ Time Frame: Baseline until death from any cause (up to approximately 42 months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
Overall surivival (OS) [ Time Frame: Baseline until death ( up to approximately 42 months) ]
Change History Complete list of historical versions of study NCT03016312 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2019)
  • Percentage of Participants who Survived at Month 12 and 24 [ Time Frame: Months 12, 24 ]
  • 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 ]
  • 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 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2017)
  • 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 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 (assessed at baseline then every 9 weeks for first 27 weeks thereafter every 12 weeks until confirmed radiographic disease progression, death, loss to follow-up, up to approximately 42 months) ]
  • Percentage of Participants Who are Radiographic Progression-Free at Month 6 and 12 [ Time Frame: Months 6, 12 ]
  • Immune-Modified rPFS, as Assessed by the Investigator [ Time Frame: Baseline until disease progression or death (assessed at baseline then every 9 weeks for first 27 weeks thereafter every 12 weeks until confirmed radiographic disease progression, death, loss to follow-up, up to approximately 42 months) ]
  • Percentage of Participants With Greater Than (>) 50% Decrease in Prostate-Specific Antigen (PSA) From Baseline [ Time Frame: Baseline up to 42 months (assessed at Screening then prior to study treatment on Day 1 of every cycle [cycle length: 21 days], until confirmed radiographic disease progression, up to 42 months) ]
  • Time to PSA Progression [ Time Frame: Baseline up to 42 months (assessed at Screening then prior to study treatment on Day 1 of every cycle (cycle length: 21 days), until confirmed radiographic disease progression, up to 42 months) ]
  • Percentage of Participant With Objective Response, as Determined by the Investigator Through use of PCWG3 Criteria and Immune Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Criteria [ Time Frame: Baseline until disease progression or death (assessed at baseline then every 9 weeks for first 27 weeks thereafter every 12 weeks until confirmed radiographic disease progression, death, loss to follow-up, up to approximately 42 months) ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 42 month ]
  • Minimum Observed Serum Concentration (Cmin) of Atezolizumab [ Time Frame: predose (0 hours[h]) on Day 1 Cycle 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); at atezolizumab discontinuation visit (30 days after last dose); and 120 days after last dose of atezolizumab up to 42 months ]
  • Maximum Observed Serum Concentration (Cmax) of Atezolizumab [ Time Frame: predose (0 h) on Day 1 Cycle 1, 2, 3, 4, 8, 12, 16 (Cycle length: 21 days); 0.5h postdose (infusion:60 minutes) on Day 1 of Cycle 1; at atezolizumab discontinuation visit (30 days after last dose); 120 days after last dose of Atezolizumab up to 42 months ]
  • Plasma Concentration of Enzalutamide [ Time Frame: predose (0 h) and 1 h postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (-1 h) on Day 1 Cycle 8; up to 42 months ]
  • Plasma Concentration of N-Desmethyl Enzalutamide [ Time Frame: predose (0 h) and 1 h postdose on Day 1 Cycle 1 and 3 (Cycle length: 21 days); pre-dose (-1 h) on Day 1 Cycle 8; up to 42 months ]
  • Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab [ Time Frame: predose (0 h) on Day 1 Cycle 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 ]
  • Percentage of Participants who Required Initiation or Increase in Opiate Analgesic use for Cancer Pain [ Time Frame: Baseline up to 42 months ]
  • Time to Initiation or Increased Opiate Analgesic Use [ Time Frame: Baseline up to 42 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostatic Neoplasms, Castration-Resistant
Intervention  ICMJE
  • 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®
Study Arms  ICMJE
  • 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).
    Interventions:
    • Drug: Atezolizumab
    • Drug: Enzalutamide
  • 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).
    Intervention: Drug: Enzalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 15, 2019)
771
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2017)
558
Estimated Study Completion Date  ICMJE March 21, 2020
Estimated Primary Completion Date March 21, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   China,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Italy,   Japan,   Korea, Republic of,   Poland,   Russian Federation,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT03016312
Other Study ID Numbers  ICMJE CO39385
2016-003092-22 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP