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

Launched by UNIVERSITY OF BRITISH COLUMBIA · Mar 19, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating whether using personalized treatment based on the genetic makeup of a patient’s prostate cancer can lead to better results. Men diagnosed with high-risk localized prostate cancer will receive a combination of medications for 8 weeks while their tumor tissue undergoes genetic testing. If their tumor can be analyzed, they will be placed in one of several treatment groups based on their genetic results, receiving either the initial treatment alone or an additional medication. The study aims to see how well these different treatment options work after surgery to remove the prostate.

To participate in this trial, men must be at least 18 years old and have confirmed high-risk prostate cancer. They should not have received any previous treatments for their cancer and must consent to genetic testing. Participants can expect to spend some time on treatment and monitoring, with a focus on how well their cancer responds. It's important to know that not everyone will qualify, as there are specific health criteria to ensure safety during the trial.

Gender

MALE

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)