Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone and Apalutamide for Rising PSA After RP (FORMULA-509)

• Status: Active, not recruiting
• Trial end date: 2024-09-30
• Target enrollment: 0
• Participant gender: Male

Summary

This research study is comparing two different combinations of androgen deprivation therapy (ADT) used together with radiation as a treatment for rising PSA after radical prostatectomy (prostate cancer).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Dana-Farber Cancer Institute
• Collaborator: Janssen Pharmaceutica
• Treatments: Abiraterone Acetate; Bicalutamide; Prednisone

Criteria

Inclusion Criteria:

• Histologically confirmed prostate cancer

• PSA ≥ 0.1 after radical prostatectomy (value w/in 3 months of registration) AND at least 1 unfavorable risk factor listed below.

• Gleason 8-10

• PSA > 0.5

• Pathologically positive lymph nodes

• pT3 or pT4

• PSA doubling time (DT) < 10 months

• Negative margins

• Persistent PSA after RP (PSA never dropped below 0.1 after RP)

• Local/regional recurrence on imaging

• Decipher "High risk" (a Medicare-reimbursed test for risk of metastases after prostatectomy)

• Candidate for salvage radiation and ADT treatment

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. Subject must have the ability to understand and willingness to sign the written informed consent document.

• 18 ≤ Age ≤ 95 at the time of consent

• ECOG Performance Status ≤ 2 (Appendix A)

• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 3 months of registration.

• System Laboratory Value

• Hematological:

• Platelet count (plt) ≥ 100,000/ µL

• Hemoglobin (Hgb) ≥ 9 g/dL

• Absolute neutrophil count (ANC) ≥ 1000 cells/µL

• Renal:

--GFR1 ≥ 45 mL/min

• Hepatic and Other:

• Bilirubin2 ≤ 1.5 × upper limit of normal (ULN)

• Aspartate aminotransferase (AST) ≤ 2.5 × ULN

• Alanine aminotransferase (ALT) ≤ 2.5 × ULN

• Serum Albumin > 3.0 g/dL

• Serum potassium ≥ 3.5 mmol/L

• Coagulation:

• International Normalized Ratio (INR)

• or Prothrombin Time (PT)

• Activated Partial Thromboplastin Time

• (aPTT) ≤ 1.5 × ULN (unless on prophylactic or therapeutic dosing with low molecular weight heparin)

• Cockcroft-Gault formula will be used to calculate creatinine clearance (see study procedure manual SPM)

• In subjects with Gilbert's syndrome, if total bilirubin is >1.5 × ULN, measure direct and indirect bilirubin; if direct bilirubin is ≤1.5 × ULN, subject may be eligible

• Agrees 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 agrees 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.

• Must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study drug.

• Ability to understand and comply with study procedures for the entire length of the study as determined by the site investigator or protocol designee

• Medications known to lower the seizure threshold (see list under prohibited meds) must be discontinued or substituted at least 4 weeks prior to study entry (Section 5.5)

• Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be discontinued prior to study entry

• Able to swallow pills

Exclusion Criteria:

• Use of post-prostatectomy ADT for > 30 continuous days prior to registration (ADT defined as use of GnRH agonist, with or without an anti-androgen). However, patients with testosterone recovery after post-prostatectomy ADT are eligible (testosterone recovery defined as total testosterone > 190 ng/dL) regardless of how long they have been on ADT.

• Prior pelvic radiation unless additional radiation can be safely delivered according to the treating physician

• PSA > 15 ng/mL in screening

• History of any of the following:

• Seizure or known condition that may predispose to seizure (e.g., prior stroke within 1 year of randomization, 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, symptomatic congestive heart failure, 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 randomization

• Current evidence of any of the following:

• Uncontrolled hypertension

• Gastrointestinal disorder affecting absorption

• Active infection (e.g., human immunodeficiency virus [HIV] or viral hepatitis)

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

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

• Moderate or severe hepatic impairment (Child Pugh Class B or C)

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, psychiatric illness or social situations that would limit compliance with study requirements

• Individuals with a history of another malignancy are not eligible if:

• the cancer is under active treatment or

• the cancer can be seen on radiology scans or

• if they are off cancer treatment but in the opinion of their oncologist have a high risk of relapse within 5 years

• Confirmed bone metastases on imaging