Randomized Phase II Study of Salvage XRT + ADT +/- Abiraterone Acetate and Apalutamide (ARN-509) for Rising PSA after Radical Prostatectomy with Adverse Features. Facilitating Optimal Radiation Management Using Leuprolide, Abiraterone Acetate, and Apalutamide (FORMULA-509 Trial)

Protocol # :
Prostate Cancer
Disease Sites
Principal Investigator
Nguyen, Paul, L
Site Investigator
Bubley, Glenn
Nguyen, Paul, L.
Orio, Peter
Orio, Peter
Site Research Nurses
Creaton, Eileen
Kemp, Joanna, H.
Mann, Eileen, Marie
Marujo, Rose
Morrissey, Mary Ellen
Pasquale, Kathryn, Mary

Trial Description

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).

Eligibility Requirements

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

- 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

- 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