Genomic testing to guide treatment for high-risk localized prostate cancer

Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer

This study is testing if personalized treatment based on genetic testing of prostate tumors can help men with high-risk localized prostate cancer do better after surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 315 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: University of British Columbia (Academic / other)
• Drugs / interventions: chemotherapy, radiation, prednisone, atezolizumab
• Locations: 9 sites (Sacramento, California and 8 other locations)
• Trial ID: NCT04812366 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of personalized therapy based on genomic testing of prostate tumor tissue in patients with high-risk localized prostate cancer. Participants will initially receive 8 weeks of treatment with a luteinizing hormone-releasing hormone agonist and apalutamide while their tumor's genomic profile is analyzed. Those with evaluable tissue will be randomized into specific treatment arms based on their genomic results, while others will continue on the initial treatment for an additional 16 weeks. The study will assess clinical responses and outcomes following radical prostatectomy.

Who should consider this trial

Good fit: Ideal candidates are males aged 18 and older with histologically confirmed high-risk localized prostate cancer.

Not a fit: Patients with low-risk prostate cancer or those with small cell differentiation in their tumors may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to more effective, tailored treatments for patients with high-risk localized prostate cancer.

How similar studies have performed: Previous studies have shown promise in using genomic profiling to guide cancer treatment, suggesting potential success for this approach.

Eligibility criteria

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 4 must be dominant, ≥50% average across 3 or more systematic cores) or
* ≥25% Gleason pattern 5 in 3 or more systematic or MRI-targeted cores (may include G4+5, or G3+5, but pattern 5 must be ≥25% average across 3 or more systematic cores).
* Gleason \> 8 or greater on minimum of one core either targeted or systematic biopsy and PSA \>20
* Participants with oligometastatic (\< 3) metastases by PSMA (Prostate-Specific Membrane Antigen) imaging only who are deemed candidates for radical prostatectomy are eligible

IV. Participants must consent to genetic testing at registration and prior to assignment by a central reference laboratory

V. No prior systemic or localized treatment for prostate cancer. Up to 30 days of LHRHa is allowable prior to treatment.

VI. ECOG (Eastern Cooperative Oncology Group) performance status 0 or 1 (Appendix II) and a life expectancy of ≥ 3 years

VII. Participants must have adequate end-organ function and all laboratory tests must be performed within 4 weeks prior to registration into master protocol.

VIII. Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrolment in the trial to document their willingness to participate.

Exclusion Criteria:

\- I. Received more than 30 days of LHRHa prior to registration and initiation of LHRHa + APA

II. Stage T4 prostate cancer by clinical examination or radiologic evaluation

III. Hypogonadism or severe androgen deficiency as defined by screening serum testosterone more than 50 ng/dL below the normal range for the institution

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;
* Uncontrolled or recent clinically significant cardiac disease, including: angina pectoris, symptomatic pericarditis, coronary artery bypass grafting, coronary angioplasty, or stenting, or myocardial infarction in the previous 12 months; history of documented congestive heart failure (New York Heart Association functional classification III-IV) or cardiomyopathy; history of any cardiac arrhythmias, e.g. ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months;
* Participants with uncontrolled hypertension

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 regimen

VIII. Severe concurrent disease, infection, or co-morbidity that, in the judgement of the Investigator, would make the participant inappropriate for enrollment or prostatectomy

IX. Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer

X. Receiving concurrent androgens, estrogens, or pregestational agents, or prior exposure to any of these agents within 6 months prior to randomization

XI. M1 by conventional imaging (CT, bone scan)

Where this trial is running

Sacramento, California and 8 other locations

• University of California Davis — Sacramento, California, United States (Recruiting)
• Brigham & Women's Hospital — Boston, Massachusetts, United States (Recruiting)
• University of Michigan Health — Ann Arbor, Michigan, United States (Recruiting)
• U.T. MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (Recruiting)
• Vancouver Prostate Centre — Vancouver, British Columbia, Canada (Recruiting)
• London Health Sciences Centre — London, Ontario, Canada (Recruiting)
• Ottawa Hospital Research Institute (OHRI) — Ottawa, Ontario, Canada (Recruiting)
• University Health Network — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Martin E Gleave, MD

Conditions Prostate Cancer