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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03016312




Registration number
NCT03016312
Ethics application status
Date submitted
9/01/2017
Date registered
10/01/2017
Date last updated
17/02/2023

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2016-003092-22
Secondary ID [2] 0 0
CO39385
Universal Trial Number (UTN)
Trial acronym
IMbassador250
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms, Castration-Resistant 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Enzalutamide

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).

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).


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg), intravenous (IV) infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: Enzalutamide
Enzalutamide capsules will be administered orally at a dose of 160 mg daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Baseline until death from any cause (up to approximately 42 months)
Secondary outcome [1] 0 0
Percentage of Participants Who Survived at Month 12 and 24
Timepoint [1] 0 0
Months 12, 24
Secondary outcome [2] 0 0
Time to First Symptomatic Skeletal Event (SSE)
Timepoint [2] 0 0
Baseline up to end of study (up to approximately 42 months)
Secondary outcome [3] 0 0
Radiographic Progression-Free Survival (rPFS), as Assessed by the Investigator and Adapted From the PCWG3 Criteria
Timepoint [3] 0 0
Baseline until disease progression or death from any cause (up to approximately 42 months)
Secondary outcome [4] 0 0
Percentage of Participants Who Are Radiographic Progression-Free, as Assessed by the Investigator and Adapted From the PCWG3 Criteria
Timepoint [4] 0 0
Months 6, 12
Secondary outcome [5] 0 0
Percentage of Participants With Greater Than (>) 50 Percent (%) Decrease in Prostate-Specific Antigen (PSA) From Baseline
Timepoint [5] 0 0
Baseline until disease progression (up to approximately 42 months)
Secondary outcome [6] 0 0
Time to PSA Progression, Assessed as Per PCWG3 Criteria
Timepoint [6] 0 0
Baseline until disease progression (up to approximately 42 months)
Secondary outcome [7] 0 0
Percentage of Participant With Objective Response, as Determined by the Investigator Through Use of PCWG3 Criteria
Timepoint [7] 0 0
Baseline until disease progression or death from any cause (up to approximately 42 months)
Secondary outcome [8] 0 0
Percentage of Participants With Adverse Events
Timepoint [8] 0 0
Baseline up to end of study (up to approximately 42 month
Secondary outcome [9] 0 0
Minimum Observed Serum Concentration (Cmin) of Atezolizumab
Timepoint [9] 0 0
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)
Secondary outcome [10] 0 0
Maximum Observed Serum Concentration (Cmax) of Atezolizumab
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
Plasma Concentration of Enzalutamide
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Plasma Concentration of N-Desmethyl Enzalutamide
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
Timepoint [13] 0 0
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

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
10/01/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
20/12/2022
Sample size
Target
Accrual to date
Final
772
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Eastern Health; Cancer Services - Box Hill
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital; Concord Cancer Centre - Concord
Recruitment hospital [3] 0 0
Macquarie University Hospital - Macquarie Park
Recruitment hospital [4] 0 0
Royal Brisbane & Women's Hosp; Cancer Care Serv - Herston
Recruitment hospital [5] 0 0
Adelaide Cancer Centre - Kurralta Park
Recruitment hospital [6] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [4] 0 0
4029 - Herston
Recruitment postcode(s) [5] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [6] 0 0
3168 - Clayton
Recruitment outside Australia
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United States of America
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California
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Colorado
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Connecticut
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Graz
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Linz
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Wien
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Aalst
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Gent
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Moscow
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Bern
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Taichung
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Taipei
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Taoyuan
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Leicester
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03016312
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03016312