Testing the Addition of the Drugs, Apalutamide and Abiraterone Acetate With Prednisone, to the Usual Hormone Therapy and Radiation Therapy After Surgery for Prostate Cancer

• Status: Suspended
• Trial end date: 2031-11-01
• Target enrollment: 0
• Participant gender: Male

Summary

This phase III trial studies how well adding apalutamide, abiraterone acetate, and prednisone to the usual hormone therapy and radiation therapy works compared to the usual hormone therapy and radiation therapy in treating patients with node-positive prostate cancer after surgery. Radiation therapy uses high energy x-ray to kill tumor cells and shrink tumors. Androgens, or male sex hormones, can cause the growth of prostate cancer cells. Drugs, such as apalutamide, may help stop or slow the growth of prostate cancer cell growth by blocking the androgens. Abiraterone acetate blocks some of the enzymes needed for androgen production and may cause the death of prostate cancer cells that need androgens to grow. Prednisone may help abiraterone acetate work better by making tumor cells more sensitive to the drug. Adding apalutamide and abiraterone acetate with prednisone to the usual usual hormone therapy and radiation therapy after surgery may stabilize prostate cancer and prevent it from spreading or extend time without disease spreading compared to the usual approach.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NRG Oncology
• Collaborator: National Cancer Institute (NCI)
• Treatments: Abiraterone Acetate; Cortisone; Hormones; Prednisone

Criteria

Inclusion Criteria:

• Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted

• Any T-stage is eligible

• Appropriate stage for study entry based on fluciclovine F-18 positron emission tomography (PET) scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease; (Note that though every effort should be made to obtain a fluciclovine F-18 PET [FACBC, Axumin] scan, if the patient has already had a recent gallium Ga 68-labeled PSMA-11 [Ga-68 PSMA] PET scan or C-11 or F-18 choline PET scan within 90 days prior to registration [to include scan report] then repeat molecular imaging with a fluciclovine F-18 PET [FACBC, Axumin] scan will not be required.)

• Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen (including external iliacs, internal iliacs, and/or obturator nodes)

• History/physical examination within 90 days prior to registration

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 90 days prior to registration

• Detectable PSA after radical prostatectomy. Detectable PSA is defined as serum PSA > 0 ng/mL at least 30 days after prostatectomy and within 90 days of registration and before start of GnRH agonist/antagonist

• Patients who have already started on post-prostatectomy GnRH agonist/antagonist for =< 45 days prior to registration are eligible (Note: patients who started on an oral antiandrogen are eligible if started =< 45 days and stopped prior to registration)

• Hemoglobin >= 9.0 g/dL, independent of transfusion and/or growth factors (within 90 days prior to registration)

• Platelet count >= 100,000 x 10^9/uL independent of transfusion and/or growth factors (within 90 days prior to registration)

• Serum potassium >= 3.5 mmol/L within 90 days prior to registration

• Creatinine clearance (CrCl) >= 30 mL/min estimated by Cockcroft-Gault (please use actual weight for calculation unless greater than 30% above ideal body weight then use the adjusted body weight) (within 90 days prior to registration)

• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert?s syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is =< 1.5 x ULN, subject is eligible) (within 90 days prior to registration)

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (within 90 days prior to registration)

• Serum albumin >= 3.0 g/dL (within 90 days prior to registration)

• Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration

• 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 (didanosine [DDI] is not permitted) with undetectable viral load within 6 months are eligible for this trial and have a CD4 count >= 200 cells/microliter within 30 days prior to registration. Note: HIV testing is not required for eligibility for this protocol

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol

• 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 30 days prior to registration

• 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) who has no evidence of disease for < 3 years must contact the principal investigator, Ron Chen, Doctor of Medicine (MD)

• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Exclusion Criteria:

• Definitive radiologic evidence of metastatic disease (M1a, M1b or M1c) on molecular imaging (e.g. fluciclovine F-18 PET, PSMA, F-18 choline 11)

• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration)

• 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

• Didanosine (DDI) antiretroviral therapy is not permitted

• History of any of the following:

• Seizure or known condition that may pre-dispose to seizure (e.g. prior stroke within 1 year prior to registration, brain arteriovenous malformation, Schwannoma, meningioma, or other benign central nervous system [CNS] or meningeal disease which may require treatment with surgery or radiation therapy)

• Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to registration

• 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

• Current evidence of any of the following:

• Known gastrointestinal disorder affecting absorption of oral medications

• Active uncontrolled infection

• 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

• Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg prednisone/prednisolone once daily

• Baseline moderate and severe hepatic impairment (Child-Pugh Class B & C)

• Inability to swallow oral pills

• Any current condition that in the opinion of the investigator, would preclude participation in this study

• Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study