Clinical trial NCT02028988: Enzalutamide + External Beam Rt For Prostate
Official title: Enzalutamide With External Beam Radiation for Intermediate Risk Prostate Cancer: A Phase II Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intermediate Risk Prostate Cancer
Keywords: Intermediate Risk Prostate Cancer
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: Medivation, Inc.
First posted: 2014-01-07
Enrollment: 64
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: * The participant will be given a study drug-dosing diary for each of 6 treatment cycles. Each treatment cycle lasts 28 days (4 weeks), during which time the participant will be taking the study drug enzalutamide by mouth (4 pills daily). The diary will also include special instructions for taking the enzalutamide.
* The participant will also be undergoing external beam radiation therapy during the study, for a duration of 8 ½-10 weeks. Treatment will be administered on an outpatient basis. This part of the study is considered standard of care.
* The participant will be required to have fiducial markers placed within the prostate as part of this study. These are very small gold markers that are placed in the prostate. This procedure is similar to the biopsy that the participant had to diagnose their cancer. This procedure is routinely performed to permit imaging and position corrections to improve the precision of the external beam (radiation) delivery (Image Guided Radiation Therapy). The placement of the three gold markers is performed by an Urologist. The fiducials are placed under ultrasound guidance. This is also considered standard of care and is not experimental.
* Planned Follow-up: Participants will be followed on study at a 3 month follow-up after treatment (cessation of enzalutamide). Additional follow-up to assess the status of the participant's cancer will be conducted at the discretion of the treating physicians as part of the participant's routine medical care.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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 infection.
* 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 seizure.
* History of loss of consciousness or transient ischemic attack within 12 months prior to enrollment.

  * 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 visit;
  * Uncontrolled hypertension as indicated by systolic blood pressure \> 170 mmHg or diastolic blood pressure \> 105 mmHg on 2 consecutive measurements at the screening visit;
  * 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 enrollment.
  * 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); ketoconazole.
  * 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.

Primary outcomes:
measure: Percentage of Participants With PSA at or Below 0.2 ng/ml
timeFrame: End of treatment, up to 27 weeks.
Secondary outcomes:
measure: Median DHEA-S
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Androstenedione
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Testosterone
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Free Testosterone
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Estrone
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Estradiol
timeFrame: Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks
measure: Median Bicep Fat Fold Measurement
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Median Tricep Fat Fold Measurement
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Median Shoulder Blade Fat Fold Measurement
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Median Waist Fat Fold Measurement
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Median Waist Circumference
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Median Weight
timeFrame: At baseline and end of treatment, up to 27 weeks
measure: Number of Participants With a Sleep Quality Score of 0 or 1
timeFrame: Measured at cycles 1, 3, and 5.
measure: Urinary Incontinence Median Score
timeFrame: Measured at cycles 1, 3, and 5.
measure: Urinary Irritation Median Score
timeFrame: Measured at cycles 1, 3, and 5.
measure: Bowel Function Median Score
timeFrame: Measured at cycles 1, 3, and 5.
measure: Sexual Function Median Score
timeFrame: Measured at cycles 1, 3, and 5.
measure: Hormone Function Median Score
timeFrame: Measured at cycles 1, 3, and 5.
measure: Number of Participants With a Fatigue Score of 3 or 4
timeFrame: Cycles 1, 3, and 5
measure: Median Collagen Type 1 C-Telopeptide
timeFrame: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks
measure: Median Bone-Specific Alkaline Phosphatase
timeFrame: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks
measure: Median Procollagen Type II Intact N Terminal Propeptide
timeFrame: Measured at baseline, end of treatment, and at 3 month follow-up, up to 40 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: Glenn Bubley, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaplan I, Bubley GJ, Bhatt RS, Taplin ME, Dowling S, Mahoney K, Werner E, Nguyen P. Enzalutamide With Radiation Therapy for Intermediate-Risk Prostate Cancer: A Phase 2 Study. Int J Radiat Oncol Biol Phys. 2021 Aug 1;110(5):1416-1422. doi: 10.1016/j.ijrobp.2021.02.027. Epub 2021 Feb 23.