Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer
University of British Columbia
Summary
The objective of this study is to see if providing an appropriate therapy based on the genomic testing of prostate tumour tissue will result in an improved clinical response. Each participant will be treated with 8 weeks of a luteinizing hormone-releasing hormone agonist (LHRHa) plus apalutamide (APA) while genome sequence characterization is being done. Participants with biopsy specimens deemed unevaluable for genomic testing will remain on LHRHa plus APA for an additional 16 weeks. Participants with evaluable tissue will be assigned to one of the open-label sub-studies on the basis of genomic profiling results. Within each group, they will be randomized to a specific treatment arm either LHRHa plus APA alone or adding abiraterone acetate and prednisone, docetaxel or niraparib. The study will evaluate the response rate and outcomes after radical prostatectomy in each arm of the trial.
Description
This is a multi-centre adaptive multi-arm phase II study. Participants are treated with an induction period of at least 8 weeks of LHRH agonist/antagonist (LHRHa) plus apalutamide (APA) while genome sequence characterization is being done. Genomic sequencing analysis will be performed centrally by Tempus, a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory. For the DNA gene profiling, formalin-fixed paraffin-embedded (FFPE) prostate cancer and surrounding healthy tissue from diagnostic biopsies will be used for genetic analysis. Copy number profiling will be performed usi…
Eligibility
- Age range
- 18+ years
- Sex
- Male
- Healthy volunteers
- No
Inclusion Criteria: \- I. Males ≥ 18 years of age II. Histologically confirmed adenocarcinoma of the prostate without pathologic evidence of small cell differentiation at the time of initial diagnosis III. High-risk localized prostate cancer as defined by: * PSA (prostate specific antigen) \>20, any GS or \>8 or * Gleason pattern 4 in 6 or more systematic cores (pattern 4 must be dominant, ≥50% average across 6 or more systematic cores) or * ≥ 50% Gleason pattern 4 in 3 or more systematic or Magnetic Resonance Imaging (MRI)-targeted cores and PSA ≥ 20 (may include G4+3 or G4+4 but pattern…
Interventions
- DrugApalutamide 60mg Tab
4 tablets by mouth once a day for 24 weeks
- DrugAbiraterone Acetate 250mg
4 tablets by mouth on an empty stomach once a day for 16 weeks
- DrugPrednisone 5mg Tab
1 tablet by mouth once daily while taking abiraterone acetate
- DrugDocetaxel
Infusion every 3 weeks for 6 cycles (each cycle has 3 weeks)
- DrugNiraparib 100mg Oral Capsule
3 capsules by mouth once daily for 16 weeks
- DrugAtezolizumab
1200mg infusion every 3 weeks for 6 cycles
Locations (9)
- University of California DavisSacramento, California
- Brigham & Women's HospitalBoston, Massachusetts
- University of Michigan HealthAnn Arbor, Michigan
- U.T. MD Anderson Cancer CenterHouston, Texas
- Fred Hutchinson Cancer CenterSeattle, Washington
- Vancouver Prostate CentreVancouver, British Columbia