Salvage Radiation Therapy with or without Enzalutamide in Treating Patients with High-Risk PSA-Recurrent Prostate Cancer after Radical Prostatectomy
- Willing and able to provide written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information * NOTE: HIPAA authorization may be either included in the informed consent or obtained separately
- Patients must have histologically confirmed adenocarcinoma of the prostate gland
- Patients must have received primary treatment with radical prostatectomy
- Patients must have evidence of biochemical (PSA) relapse after prostatectomy, defined by one rise in PSA above a baseline detectable value (>= 0.05 ng/mL) using measurements taken at least 4 weeks apart from each other (all PSA values must be within 12 months of study entry)
- Patients must have pathological Gleason (pG) sum 8-10; or pG sum 7 and either pT3 or R1 disease (i.e. positive margins)
- Patients must have an absolute PSA level between >= 0.05 and < 0.7 ng/mL at the time of study entry
- Patients must have non-metastatic (M0) disease, as defined by a lack of metastases seen on computed tomography (CT) scan of the chest/abdomen/pelvis and whole-body radionuclide 99Tc (technetium-99) bone scan, (or sodium fluoride positron emission tomography [PET] scan) taken within 3 months of study entry
- Patients must have had node negative (pN0) disease found at the time of surgery; if a nodal dissection was not performed at the original surgery then patients must be N0, as defined by a lack of radiographic or clinical evidence of local-regional tumor recurrence, including pelvic lymph nodes >= 2 cm in short-axis diameter
- Patients must have non-castrate levels of serum testosterone (>= 150 ng/dL)
- Patients must not have previously received hormonal therapy (luteinizing hormone-releasing hormone [LHRH] agonist, antiandrogen, or both), with the exception of neoadjuvant or adjuvant hormones given in conjunction with prostatectomy; in such cases, hormone therapy must have been administered for =< 6 months, discontinued >= 6 months ago, and serum testosterone must be >= 150 ng/dL
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and life expectancy >= 3 years
- White blood cells (WBC) >= 3000/mm^3 within 4 weeks of enrollment
- Granulocytes >= 1500/mm^3 within 4 weeks of enrollment
- Hemoglobin >= 9 g/dL within 4 weeks of enrollment
- Platelets >= 100,000/mm^3 within 4 weeks of enrollment
- Bilirubin =< 1.8 mg/dL within 4 weeks of enrollment
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 times the institutional upper limit of normal within 4 weeks of enrollment
- Creatinine =< 1.8 mg/dL OR a calculated creatinine clearance >= 60 mL/hr within 4 weeks of enrollment
- Patients must be disease-free from prior malignancies for >= 3 years, with the exception of non-melanoma skin cancers and superficial urothelial cancers
- Patients must have the ability to swallow the study drug whole as a tablet or capsule
- Throughout study, male patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) starting at screening and continuing throughout the study period and for 3 months after final study drug administration or per local guidelines where these require additional description of contraceptive methods; two acceptable methods of birth control thus include the following: * Condom (barrier method of contraception); AND * One of the following is required: ** Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner ** Placement of an intrauterine device or intrauterine system by the female partner ** Additional barrier method: occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner ** Tubal ligation in the female partner ** Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), for > 6 months
- Throughout the study, patients must use a condom if having sex with a pregnant woman
- The patient was informed about the positive survival results of the RTOG 96-01 clinical trial, and has elected to forgo treatment with high-dose bicalutamide
- Currently active second malignancy
- Primary treatment with radiation therapy
- Radiographic or clinical evidence of regional tumor nodal recurrence, including pathological pelvic lymph nodes >= 2 cm in short-axis diameter; radiographic evidence of distant metastases is also an exclusion
- Concurrent use of other antiandrogens, estrogen-like agents, or 5a-reductase inhibitors
- Use of systemic corticosteroids equivalent to prednisone 10 mg/day or higher at the time of study entry (inhaled corticosteroids are permitted)
- Concurrent use of other anti-cancer agents or treatments
- Serious concurrent medical illnesses (including uncontrolled major cardiac, pulmonary, Child-Pugh C liver or psychiatric diseases) or active major infections (including human immunodeficiency virus [HIV], hepatitis A-C)
- Clinically significant cardiovascular disease including: * Myocardial infarction within 6 months of screening visit * Uncontrolled angina within 3 months of screening visit * Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, or history of anthracycline or anthracenedione (mitoxantrone) treatment, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within three months of the screening visit results in a left ventricular ejection fraction that is >= 45% * History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsade de pointes) * Prolonged corrected QT interval by the Fridericia correction formula (QTcF) on the screening electrocardiogram (ECG) > 470 msec * History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place * Hypotension (systolic blood pressure < 86 mmHg or bradycardia with a heart rate of < 50 beats per minute on the screening ECG, unless pharmaceutically induced and thus reversible [i.e. beta blockers]) * Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg at the screening visit
- Medications which lowers seizure threshold
- History of seizure or any condition that may predispose to seizure including, but not limited to underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism; also, history of loss of consciousness or transient ischemic attack within 12 months of enrollment (day 1 visit)
- Patients taking medications that may have adverse interactions with enzalutamide
District of Columbia
I. The rate of freedom-from-PSA-progression (FFPP).
I. Local recurrence within the radiation field (confirmed pathologically).
II. Metastasis-free survival (MFS) rates.
III. Safety, feasibility, and tolerability as assessed by National Cancer Institute (NCI) Common Toxicity Scales (version [v]4.0), quality of life (Expanded Prostate Cancer Index Composite [EPIC] survey), and achievement of accrual goals.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive placebo orally (PO) once daily (QD) for 6 months. Beginning on day 61, patients also undergo 3 dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) 5 days a week (Monday-Friday) for up to 8 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive enzalutamide PO QD for 6 months. Beginning on day 61, patients also undergo 3D-CRT or IMRT as in Arm I. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for up to 42 months.
Trial Phase Phase II
Trial Type Treatment
Johns Hopkins University / Sidney Kimmel Cancer Center
Phuoc Tho Tran
- Primary ID J1454
- Secondary IDs NCI-2015-00621, c14-138, CIR00007200
- Clinicaltrials.gov ID NCT02203695