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Salvage Radiation Therapy with or without Enzalutamide in Treating Patients with High-Risk PSA-Recurrent Prostate Cancer after Radical Prostatectomy

Trial Status: Active

This randomized phase II trial studies how well salvage radiation therapy with or without enzalutamide works in treating patients with prostate cancer with high-risk prostate cancer with a rising prostate-specific antigen (PSA) after surgery to remove the entire prostate and some of the tissue around it (radical prostatectomy). Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Enzalutamide may stop the growth of prostate cancer by blocking an important protein that keeps prostate cancer cells alive and may make prostate cells more resistant to radiation therapy. It is not yet known whether salvage radiation therapy is more effective with or without enzalutamide in treating prostate cancer.

Inclusion Criteria

  • 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 (e.g., 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

Exclusion Criteria

  • 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

Sibley Memorial Hospital
Status: ACTIVE
Contact: Ashley Bruns
Phone: 202-537-4000


University of Chicago Comprehensive Cancer Center
Contact: Stanley Lawrence Liauw


IU Health Arnett Cancer Care
Status: ACTIVE
Contact: Bamidele A Adesunloye
Phone: 765-838-6885


Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Phuoc Tho Tran
Phone: 410-614-3880
Suburban Hospital
Status: ACTIVE
Contact: Stephen C. Greco
Phone: 301-896-2012


Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: ACTIVE
Contact: Daniel Eidelberg Spratt
Wayne State University / Karmanos Cancer Institute
Status: ACTIVE
Contact: Elisabeth Iljas Heath


OHSU Knight Cancer Institute-East Portland
Contact: Arthur Y. Hung


UT Southwestern / Simmons Cancer Center-Dallas
Contact: Neil B. Desai


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

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Phuoc Tho Tran

  • Primary ID J1454
  • Secondary IDs NCI-2015-00621, c14-138, CIR00007200
  • ID NCT02203695