(NRG-GU009) Parallel Phase III Randomized Trials For High Risk Prostate Cancer Evaluating De-Intensification For Lower Genomic Risk And Intensification Of Concurrent Therapy (Predict-Rt*)

For high-risk prostate cancer, a low gene risk score and plan to receive radiation therapy, is a shorter hormone therapy treatment as effective at controlling the cancer compared to the usual 24 month hormone therapy treatment?

For high-risk prostate cancer, a high gene risk score and plan to receive radiation therapy, does adding a new hormone therapy drug to the usual treatment increase the length of time without the prostate cancer spreading as compared to the usual treatment?

The purpose of this study is to find out if these approaches are better, similar, or worse than the usual approach for a type of prostate cancer. The usual treatment is defined as the care most people get for prostate cancer.

The usual approach for patients who are not in a study is treatment with hormonal drugs, approved by the Food and Drug Administration (FDA), and radiation therapy. For patients who get the usual approach for this cancer, about 70 out of 100 are free of cancer after 5 years.

This study has public funding from the National Cancer Institute (NCI), part of the National Institutes of Health (NIH) in the United States Department of Health and Human Services.

Inova Schar Cancer Institute and the Saville Cancer Screening and Prevention Center
A department of Inova Fairfax Hospital
8081 Innovation Park Dr.
Fairfax, VA 22031

• Pathologically proven diagnosis of adenocarcinoma of prostate cancer
• High-risk disease defined as having at least one or more of the following:
  • PSA>20 ng/mL prior to starting ADT
  • cT3a-T4 by digital exam or imaging (AJCC 8th Ed.)
  • Gleason Score of 8-10
  • Node positive by conventional imaging with a short axis of at least 1.0 cm
• No definitive evidence of bone metastases (M0) on bone scan or NaF PET within 120 days prior to registration
• Adults 18 years of age or older
• Adequate hematologic function
• Adequate renal function
• Adequate hepatic function
• The patient must agree to use a condom (even men with vasectomies) and another effective method of birth control if he is having sex with a woman of childbearing potential or agree to use a condom if he is having sex with a woman who is pregnant while on study drug and for 3 months following the last dose of study drug.
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial and have a CD4 count ≥ 200 cells/microliter within 60 days prior to registration. Note: HIV testing is not required for eligibility for this protocol. Of note, for patients with HIV in the intensification trial randomized to apalutamide, HAART may need to be adjusted to medications that do not interact with apalutamide.
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable after or on suppressive therapy within 60 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Note: Any patient with a cancer (other than keratinocyte carcinoma or carcinoma in situ or low-grade non-muscle invasive bladder cancer) who has been disease-free for less than 3 years must contact the Principal Investigator.
• Additional eligibility in protocol.

• Definitive radiologic evidence of metastatic disease outside of the pelvic nodes
• Prior systemic chemotherapy within ≤3 years prior to registration; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)
• Prior radical prostatectomy
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Current use of 5-alpha reductase inhibitor. NOTE: If the alpha reductase inhibitor is stopped prior to randomization the patient is eligible.
• History of any of the following:
  • Seizure disorder;
  • Current severe or unstable angina;
  • New York Heart Association Functional Classification III/IV (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification.)
  • History of any condition that in the opinion of the investigator, would preclude participation in this study
• Active uncontrolled infection requiring IV antibiotics
• Baseline severe hepatic impairment (Child Pugh Class C)
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 60 days prior Note: Apalutamide may interfere with HCV drugs. Patients on HCV medications should alert their infectious diseases physician if they get randomized to apalutamide due to the possibility that apalutamide can affect the bioavailability of some HCV medications. HCV viral testing is not required for eligibility for this protocol
• Evidence of known gastrointestinal disorder affecting absorption of oral medications
• Presence of uncontrolled hypertension (persistent systolic blood pressure [BP] ≥160 mmHg or diastolic BP ≥100 mmHg). Subjects with a history of hypertension are allowed, provided that BP is controlled to within these limits by anti-hypertensive treatment.
• Additional ineligibility in protocol.

For additional information, please go to: https://clinicaltrials.gov/ct2/show/NCT04513717