Prostate CancerPhase 2GUNSNCT04812366
Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer
A Phase 2 study testing Apalutamide 60mg Tab, Abiraterone Acetate 250mg and Prednisone 5mg Tab in people with Prostate Cancer, run by University of British Columbia at 9 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Apalutamide 60mg Tab, Abiraterone Acetate 250mg and Prednisone 5mg Tab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 315 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 21 Sep 2021to 1 Jun 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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
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- 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.
- 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).
- 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.
- 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).
- 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.
- Archival tissue must be available for genetic analysis.
Who cannot join
- Participants will be excluded if ANY of the following criteria are met:
- 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:
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- Severe or unstable angina, symptomatic pericarditis, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease, coronary artery bypass grafting, coronary angioplasty, stenting, or myocardial infarction; uncomplicated deep vein thrombosis is not considered exclusionary).
- History of any cardiac arrhythmias that preclude prostatectomy or treatment with study drugs, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality.
- 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).
- Participants with a history of hypersensitivity to any of the study drugs or any excipient.
- 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.
- Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.
- Receiving concurrent androgens, estrogens, or progestational agents, or received any of these agents within the 6 months prior to registration.
- 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.
Trial locations and contacts
9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
Doron Berlin contact
9 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
University of Michigan Health
Ann Arbor, Michigan, 48109-5946
Main Line, 800-962-3555, canceranswerline@umich.edu
Todd Morgan, MD
- Recruiting
Dana-Farber Cancer Institute / Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Daniella Furtado, 617-525-8782, Daniella_Furtado@dfci.harvard.edu
Himisha Beltran, MD
- Recruiting
U.T. MD Anderson Cancer Center
Houston, Texas, 77030
askMDAnderson, 877-632-6789, askmdanderson@mdanderson.org
Brian Chapin, M.D.
- Recruiting
University of California Davis
Sacramento, California, 95817
Mark Cokee, 916-734-8603, Mcokee@health.ucdavis.edu
Marc Dall'Era, MD
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Michael Schweizer, M.D., 206-606-6252, schweize@uw.edu
Michael Schweizer, MD
Canada4 sites, 4 recruiting
- Recruiting
London Health Sciences Centre
London, Ontario, N6A 5W9
Yoonbee Kim, 519-685-8500 ext. 56916, yoonbee.kim@lhsc.on.ca
Brant Inman, MD
- Recruiting
Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, K1H 8L6
Pascale Juneau, 613-737-8899 ext. 71064, pjuneau@ohri.ca
Rodney Breau, MD
- Recruiting
University Health Network
Toronto, Ontario, M5G 2C4
Jenny Su, 416-946-4501 ext. 3141, Jenny.su@uhn.ca
Neil Fleshner, M.D.
- Recruiting
Vancouver Prostate Centre
Vancouver, British Columbia, V5Z 1M9
Jonathan Ma, 16048755675, jma@prostatecentre.com
Martin E Gleave, MD
About this study
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.
Read more
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.
Read the detailed 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 using array Comparative Genomic Hybridisation (aCGH). Targeted sequencing using MiSeq (Illumina) and Ion Proton (Life Technologies) platforms will be performed to identify mutations in a panel of 648 genes.
Based on previous studies, we conservatively expect up to 25% of unevaluable needle biopsy specimens with inadequate/insufficient tumor tissue for genome sequencing. The patients with unevaluable tissue will continue on the master protocol (LHRHa + APA) for an additional 16 weeks followed by radical prostatectomy.
The genomically evaluable patients will be assigned to a specific sub-protocol according to the results of the genomic profile and randomized to a treatment arm within the sub-protocol for 16 weeks, with additional inclusion and exclusion criteria specified in dedicated sub-protocols. Radical prostatectomy will follow sub-protocol treatment.
Sub-protocol 1 - AR axis: No targetable actionable aberration; presence of TMPRSS2-ERG fusion, CHD1 loss or SPOP mutations: (~50% expected prevalence in study population) randomized to:
- LHRHa + APA for 16 weeks or
- LHRHa + APA + AAP (Abiraterone Acetate + Prednisone) for 16 weeks
Sub-protocol 2 - Loss of tumour suppressor genes - PTEN, TP53 or TB loss (~40%, bad prognosis) randomized to:
- LHRHa + AAP for 16 weeks or
- LHRHa + AAP + docetaxel for 6 cycles
Sub-protocol 3 - DNA damage response alterations (e.g. BRCA1/2, ATM, FANCONI, CDK12) in 6-8% assigned to:
- LHRHa + AAP + PARP (Poly [ADP-ribose] polymerase) inhibitors (niraparib) for 16 weeks
Sub-protocol 4 - Hypermutation, microsatellite instability (MSI), Lynch syndrome or CDK12 in less than 5% assigned to:
- LHRHa + APA plus PD-L1 inhibitor (atezolizumab) for 16 weeks
- This arm is closed to enrollment
Sub-Protocol 5 - cancers primed for lineage plasticity: Loss of function DNA alteration in TP53 or RB1 and/or evidence of stem cell or neuroendocrine (NE) features (~20%) assigned to:
- LHRHa + AAP + tazemetostat for 16 weeks
***This arm is closed to enrollment
Sub-protocol 6 - favorable genomic alterations as defined in SP-1, or PTENdef/AKTgain alterations (20%), will be assigned to SP-6a and SP-6b respectively, and receive
- LHRHa + AAP + capivasertib (CAPIVA) for 16 weeks
- Conditions
- Prostate Cancer
- Being tested
- Apalutamide 60mg Tab, Abiraterone Acetate 250mg, Prednisone 5mg Tab, Docetaxel, Niraparib 100mg Oral Capsule
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apalutamide 60mg TabDrug
4 tablets by mouth once a day for 24 weeks
Abiraterone Acetate 250mgDrug
4 tablets by mouth on an empty stomach once a day for 16 weeks
Prednisone 5mg TabDrug
1 tablet by mouth once daily while taking abiraterone acetate
DocetaxelDrug
Infusion every 3 weeks for 6 cycles (each cycle has 3 weeks)
Niraparib 100mg Oral CapsuleDrug
3 capsules by mouth once daily for 16 weeks
AtezolizumabDrug
1200mg infusion every 3 weeks for 6 cycles
Tazemetostat PillDrug
200 mg 4 tablets by mouth twice daily with or without food for 16 weeks
CapivasertibDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Group 1a | Active comparator | LHRHa plus apalutamide. Receives: Drug: Apalutamide 60mg Tab |
| Group 1b | Active comparator | LHRHa plus apalutamide plus abiraterone acetate plus prednisone. Receives: Drug: Apalutamide 60mg Tab; Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab |
| Group 2a | Active comparator | LHRHa plus abiraterone acetate plus prednisone. Receives: Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab |
| Group 2b | Active comparator | LHRHa plus abiraterone acetate plus prednisone plus docetaxel. Receives: Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Docetaxel |
| Group 3 | Active comparator | LHRHa plus abiraterone acetate plus prednisone plus niraparib Receives: Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Niraparib 100mg Oral Capsule |
| Group 4 | Active comparator | LHRHa plus apalutamide plus atezolizumab Receives: Drug: Apalutamide 60mg Tab; Drug: Atezolizumab |
| Group 5 | Active comparator | LHRHa plus abiraterone acetate plus prednisone plus tazemetostat Receives: Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Tazemetostat Pill |
| Group 6 | Active comparator | LHRHa plus abiraterone acetate plus prednisone plus Capivasertib Receives: Drug: Abiraterone Acetate 250mg; Drug: Prednisone 5mg Tab; Drug: Capivasertib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Pathologic Response (pCR)
Pathological Minimal Residual Disease (pMRD): pathological minimal residual disease (pMRD) is defined as residual tumour 5mm or less.
Measured: 6 years
Pathological Minimal Residual Disease (pMRD)
Pathological minimal residual disease is defined as residual tumour 5 mm or less.
Measured: 6 years
Secondary outcomes (3)
Pain level assessment
The Brief Pain Inventory-Short Form (BPI-SF) is a 9-item, self administered questionnaire which evaluates the severity of a participant's level of pain and impact on daily functioning. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks), as well as the End of Treatment (EoT) visit.
Measured: 6 years
Generic Quality of Life (QoL)
The EQ-5D-5L is a widely used instrument developed in Europe to evaluate the generic quality of life. The EQ-5D-5L has two components: the EQ-5D descriptive system and the EQ visual analogue scale. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks) as well as at the EoT visit.
Measured: 6 years
Quality of Life-Prostate Cancer Patients
This will be measured using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. The FACT-P is a multidimensional, self-report QoL instrument specifically designed for use with patients who have prostate cancer. This questionnaire will be administered at screening, prior to receiving master protocol therapy (0 weeks), the end of receiving therapy (8 weeks) as well as at the EoT visit.
Measured: 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2021
- Study start21 Sep 2021
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 315 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen Inc., University Health Network, Toronto
- Responsible party
- Principal investigator, Martin Gleave, University of British Columbia
- Investigators
- Martin E Gleave, MD, Study chair, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04812366
- Sponsor's protocol ID
- H20-03434
- Acronym
- GUNS
- Status last verified
- Jul 2026
- First submitted
- 12 Mar 2021
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No