Enzalutamide + External Beam Rt For Prostate
Phase: Phase 2
Diagnosis: Prostate Cancer
NCT ID: NCT02028988
(View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-444
This research study is evaluating a drug called enzalutamide in combination with external beam radiation therapy as a possible treatment for prostate cancer. Presently, when participants receive hormonal therapy with radiation therapy for prostate cancer, medications are given to reduce testosterone levels in the blood stream. This leads to side effects such as loss of sex drive, erectile dysfunction (ED) and decrease in muscle strength. The purpose of this study is test another form of hormonal therapy with radiation therapy. The medication called enzalutamide will be used with radiation therapy. Instead of lowering testosterone, enzalutamide blocks testosterone in cells. This study will test if enzalutamide when used with radiation will lower the PSA without causing the side effects associated with medications that lower testosterone in the blood stream.
Beth-Israel Deaconess Medical Center, Dana-Farber Cancer Institute, Brigham and Women's Hospital
Paul Nguyen, MD,
Brigham and Women's Hospital
Glenn Bubley, MD,
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute:
Judith Prisby, 617-632-5068,
Dana-Farber Cancer Institute:
Amanda Fredericks, 617-632-5514,
Dana-Farber Cancer Institute:
Meghara Walsh, 617-632-5264,
- Study population: Participants must have histologically confirmed malignancy and are
candidates for external beam radiation therapy. Patients eligible for this study must
have intermediate risk disease defined as PSA values between 10-20 ng/ml and/or T2b-c
and/or Gleason grade 7. If all three are present, less than 50% of the core biopsies
can be positive.
- Patients previously diagnosed with low risk (Gleason score < 6, clinical stage < T2a,
and PSA< 10) prostate cancer undergoing active surveillance who are re-biopsied and
found to have intermediate risk disease according to the protocol criteria are
eligible for enrollment within 180 days of the repeat biopsy procedure.
- Age 18 years or more.
- Life expectancy of greater than 1 year.
- ECOG performance status ≤ 2 (see Appendix D).
- Participants must have normal organ and marrow function as defined below:
- Leukocytes ≥3,000/mcL
- Platelets ≥80,000/mcL
- Total bilirubin < 2X institutional upper limit
- AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
- Creatinine < 2x institutional limits .
- The effects of enzalutamide on the developing human fetus are unknown. For this
reason and because enzalutamide may be teratogenic, men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation.
Ability to understand and the willingness to sign a written informed consent
- Patients must NOT meet any of the following exclusion criteria
- Received an investigational agent within 4 weeks prior to enrollment
- Stage T4 prostate cancer by clinical examination or radiologic evaluation.
- Hypogonadism or severe androgen deficiency as defined by screening serum
testosterone less than 50 ng/dL below the normal range for the institution.
- Prior androgen deprivation, chemotherapy, surgery, or radiation for prostate cancer.
- Receiving concurrent androgens, anti-androgens, estrogens, or progestational agents,
or received any of these agents within the 6 months prior to enrollment or having
taken finasteride or dutasteride within 30 days of registration.
- History of another active malignancy within the previous 5 years other than
curatively treated nonmelanomatous skin cancer and superficial bladder cancer.
Participants treated for malignancy with no relapse within two years are eligible to
participate in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
- Severe concurrent disease, infection, or co-morbidity that, in the judgment of the
Investigator, would make the patient inappropriate for enrollment.
- Unwilling to use contraceptives while on study if relevant to patient.
- History of seizure or any condition or concurrent medication that may predispose to
- History of loss of consciousness or transient ischemic attack within 12 months prior
- Clinically significant cardiovascular disease, including:
- Myocardial infarction within 3 months of enrollment;
- Uncontrolled angina within 3 months of enrollment;
- Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or
history of congestive heart failure NYHA class 3 or 4 in the past, unless a
screening echocardiogram or multi-gated acquisition scan performed within 3
months results in a left ventricular ejection fraction ≥ 45%;
- History of clinically significant ventricular arrhythmias (e.g., ventricular
tachycardia, ventricular fibrillation, torsades de pointes);
- History of Mobitz II second degree or third degree heart block without a
permanent pacemaker in place;
- Hypotension as indicated by systolic blood pressure < 86 mmHg on 2 consecutive
measurements at the Screening visit;
- Bradycardia as indicated by a heart rate < 50 beats per minute at the Screening
- Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or
diastolic blood pressure > 105 mmHg on 2 consecutive measurements at the
- EKG demonstrating equal to or greater than grade III toxicity according the NCI
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
- History of gastrointestinal disorders (medical disorders or extensive surgery)
that may interfere with the absorption of oral study drug(s) within 3 months of
- Major surgery within 4 weeks of registration.
- Previous use, or participation in a clinical trial, of an investigational agent
that blocks androgen synthesis (e.g., abiraterone acetate, TAK-700, TAK-683,
TAK-448) or targets the androgen receptor (e.g., enzalutamide, BMS 641988);
- Any condition or reason that, in the opinion of the Investigator, interferes
with the ability of the patient to participate in the trial, places the patient
at undue risk, or complicates the interpretation of safety data.
- Need for any of the medications on the list of drugs to be used with caution or
to be avoided (see APPENDIX F).
- Use of herbal or alternative remedies that may affect hormonal status such as
Prostasol or PC-SPES.