Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer
GUNS
1 other identifier
interventional
315
2 countries
9
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 prostate-cancer
Started Sep 2021
Typical duration for phase_2 prostate-cancer
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 12, 2021
CompletedFirst Posted
Study publicly available on registry
March 23, 2021
CompletedStudy Start
First participant enrolled
September 21, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
July 31, 2026
July 1, 2026
5.7 years
March 12, 2021
July 29, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Complete Pathologic Response (pCR)
Pathological Minimal Residual Disease (pMRD): pathological minimal residual disease (pMRD) is defined as residual tumour 5mm or less.
6 years
Pathological Minimal Residual Disease (pMRD)
Pathological minimal residual disease is defined as residual tumour 5 mm or less.
6 years
Secondary Outcomes (3)
Pain level assessment
6 years
Generic Quality of Life (QoL)
6 years
Quality of Life-Prostate Cancer Patients
6 years
Study Arms (8)
Group 1a
ACTIVE COMPARATORLHRHa plus apalutamide.
Group 1b
ACTIVE COMPARATORLHRHa plus apalutamide plus abiraterone acetate plus prednisone.
Group 2a
ACTIVE COMPARATORLHRHa plus abiraterone acetate plus prednisone.
Group 2b
ACTIVE COMPARATORLHRHa plus abiraterone acetate plus prednisone plus docetaxel.
Group 3
ACTIVE COMPARATORLHRHa plus abiraterone acetate plus prednisone plus niraparib
Group 4
ACTIVE COMPARATORLHRHa plus apalutamide plus atezolizumab
Group 5
ACTIVE COMPARATORLHRHa plus abiraterone acetate plus prednisone plus tazemetostat
Group 6
ACTIVE COMPARATORLHRHa plus abiraterone acetate plus prednisone plus Capivasertib
Interventions
4 tablets by mouth on an empty stomach once a day for 16 weeks
1 tablet by mouth once daily while taking abiraterone acetate
200 mg 2 tablets by mouth twice a day with or without food on an intermittent dosing schedule (days 1-4, then 3 days off) each week for 16 weeks
Eligibility Criteria
You may qualify if:
- 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. Screening biopsy must be performed within 4 months of the screening visit.
- iii. High-risk localized prostate cancer as defined by at least one of the following:
- Any combination of Gleason Score 4+3=7 and Gleason Score 8 (4+4 or 5+3) in ≥6 systematic cores (with ≥1 core Gleason Score 8 \[4+4 or 5+3\] included);
- Any combination of Gleason Score 4+3 and Gleason Score 8 (4+4 or 5+3) in ≥3 systematic cores and PSA ≥20 ng/mL (with at least 1 core Gleason Score 8 \[4+4 or 5+3\] included);
- Gleason Score ≥9 in at least 1 systematic or targeted core;
- At least 2 systematic or targeted cores with Gleason Score ≥8, each with at least 80% involvement"; or
- Gleason Score 4+3=7 in at least 6 systematic or targeted cores and PSA ≥20 ng/mL iv. Participants must provide consent blood collection and evaluation of diagnostic prostate tissue for genetic testing at registration and prior to assignment by a central reference laboratory.
- v. No prior systemic or localized treatment for prostate cancer (exception: up to 12 weeks of luteinizing hormone-releasing hormone agonist or antagonist (LHRHa) and bicalutamide is allowable prior to registration).
- vi. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix II) and a life expectancy of ≥ 3 years in the opinion of the treating oncologist.
- vii. Laboratory Requirements: Participants must have adequate end-organ function and all laboratory tests must be performed within 8 weeks prior to registration into master protocol (Table 1).
- viii. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to registration in the trial to document their willingness to participate.
- ix. Archival tissue must be available for genetic analysis.
You may not qualify if:
- Participants will be excluded if ANY of the following criteria are met:
- i. Received more than 12 weeks of LHRHa prior to registration. ii. Stage T4 prostate cancer by clinical examination or radiologic evaluation. iii. Hypogonadism or severe androgen deficiency as determined by the treating physician, or screening serum testosterone less than 50 ng/dL (1.7 nmol/L) iv. Participants with serious illnesses or medical conditions which could cause unacceptable safety risks or would not permit the participant to be managed according to the protocol. This includes but is not limited to:
- Active infection or chronic liver disease requiring systemic therapy;
- Active or known human immunodeficiency virus (HIV) with detectable viral load;
- Participants with uncontrolled hypertension or diabetes.
- Uncontrolled or recent clinically significant cardiac disease, including history of any of the following within 12 months prior to screening:
- History of any cardiac arrhythmias that preclude prostatectomy or treatment with study drugs, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality.
- v. Participants who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- vi. Participants with a history of hypersensitivity to any of the study drugs or any excipient.
- vii. Participants with a history of non-compliance to medical regimens. viii. Severe concurrent disease, infection, or co-morbidity that, in the judgment of the Investigator, would make the participant inappropriate for registration or prostatectomy.
- ix. Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.
- x. Receiving concurrent androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to registration.
- xi. M1 by conventional imaging (CT, bone scan) or PSMA-PET. Participants with oligometastatic (\<3) metastases by PSMA imaging only who are deemed candidates for radical prostatectomy are eligible.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of British Columbialead
- Janssen Inc.collaborator
- University Health Network, Torontocollaborator
Study Sites (9)
University of California Davis
Sacramento, California, 95817, United States
Dana-Farber Cancer Institute / Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115, United States
University of Michigan Health
Ann Arbor, Michigan, 48109-5946, United States
U.T. MD Anderson Cancer Center
Houston, Texas, 77030, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98109, United States
Vancouver Prostate Centre
Vancouver, British Columbia, V5Z 1M9, Canada
London Health Sciences Centre
London, Ontario, N6A 5W9, Canada
Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, K1H 8L6, Canada
University Health Network
Toronto, Ontario, M5G 2C4, Canada
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Martin E Gleave, MD
University of British Columbia
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator/Study Chair
Study Record Dates
First Submitted
March 12, 2021
First Posted
March 23, 2021
Study Start
September 21, 2021
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
July 31, 2026
Record last verified: 2026-07