IRB Study Number 20-451
Status Recruiting
Phase Phase 3
Location Akron General
Institute Taussig Cancer Institute
Description
Primary Objective
Compare metastasis-free survival (MFS) of salvage RT and GnRH agonist/antagonist vs. RT/ GnRH agonist/antagonist with abiraterone acetate with prednisone and apalutamide for patients with pathologic node-positive prostate cancer after radical prostatectomy with detectable PSA.
Secondary Objectives
1 Compare health-related quality of life (EPIC-26, EQ-5D-5L, Brief Pain Inventory, PROMIS-Fatigue) among the treatment arms.
2 Compare overall survival, biochemical progression-free survival, time to local-regional progression, time to castrate resistance, and cancer-specific survival among the treatment arms.
3 Compare the short-term and long-term treatment-related adverse events among the treatment arms.
Exploratory Objectives
1 Validate Decipher score for an exclusively node-positive population and use additional genomic information from Affymetrix Human Exon 1.0st array to develop and validate novel prognostic and predictive biomarkers.
2 Validate the PAM50-based classification of prostate cancer into luminal A, luminal B, and basal subtypes as prognostic markers and determine whether the luminal B subtype is a predictive marker for having a larger improvement in outcome from the addition of abiraterone acetate with prednisone and apalutamide.
3 To optimize quality assurance methodologies and processes for radiotherapy and imaging with machine learning strategies.
Inclusion Criteria
1 Pathologically (histologically) proven diagnosis of prostate adenocarcinoma. Any type of radical prostatectomy is permitted, including retropubic, perineal, laparoscopic or robotically assisted;
2 Any T-stage is eligible (AJCC 8th ed);
3 Appropriate stage for study entry based on Fluciclovine F-18 PET scan (FACBC, Axumin) within 90 days prior to registration that is negative for distant metastatic (M1a, M1b, M1c) disease (see Appendix IV for molecular imaging guidelines); [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 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.]
4 Pathologically node positive disease with nodal involvement only in the pelvis in the prostatectomy specimen (including external iliacs, internal iliacs, and/or obturator nodes);
5 History/physical examination within 90 days prior to registration;
6 Age ≥ 18;
7 ECOG Performance Status of 0-1 within 90 days prior to registration;
8 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 (see Section 9).
9 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);
10 Adequate hematologic function within 90 days prior to registration defined as follows:
• Hemoglobin ≥9.0 g/dL, independent of transfusion and/or growth factors
• Platelet count ≥100,000 x 109/μL independent of transfusion and/or growth factors
11 Serum potassium ≥3.5 mmol/L within 90 days prior to registration;
12 Adequate renal function within 90 days prior to registration defined as follows:
• 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) Creatinine Clearance (mL/min) = [140-Age (years)] x Weight (kg) 72 x serum creatinine (mg/dL)
13 Adequate hepatic function within 90 days prior to registration defined as follows:
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (Note: In subjects with Gilbert’s syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin and if direct bilirubin is ≤1.5 × ULN, subject is eligible)
• AST(SGOT) or ALT(SGPT) ≤2.5 × institutional ULN
• Serum albumin ≥3.0 g/dL
14 Discontinue or substitute concomitant medications known to lower the seizure threshold at least 30 days prior to registration (see list under prohibited medications in Section 5.3).
15 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.
16 Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy (didanosine (DDI) is not permitted see 5) 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.
17 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.
18 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.
19 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, MD.
20 The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.
Exclusion Criteria
1 Definitive radiologic evidence of metastatic disease ((M1a, M1b or M1c) on molecular imaging (e.g. Fluciclovine F-18 PET, PSMA, F-18 choline 11);
2 Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowed (completed > 3 years prior to registration);
3 Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields;
4 Current use of 5-alpha reductase inhibitor. NOTE: if the alpha reductase inhibitor is stopped prior to randomization the patient is eligible.
5 Didanosine (DDI) antiretroviral therapy is not permitted;
6 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 CNS or meningeal disease which may require treatment with surgery or radiation therapy)
• Severe or unstable angina, myocardial infarction, arterial or venous thromboembolic events (eg, 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
7 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 (ChildPugh Class B & C)
• Inability to swallow oral pills
• Any current condition that in the opinion of the investigator, would preclude participation in this study
8 Patients must not plan to participate in any other therapeutic clinical trials while receiving treatment on this study.
9 Patients with inflammatory bowel disease.
