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Enzalutamide + External Beam Rt For Prostate

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Glenn Bubley, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT02028988
First received: December 16, 2013
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Intermediate Risk Prostate Cancer
Drug: Enzalutamide
Radiation: External Beam Radiation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Enzalutamide With External Beam Radiation for Intermediate Risk Prostate Cancer: A Phase II Study

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • PSA level after 6 months of enzalutamide therapy [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    PSA level of less than or equal to 0.2 ng/ml at the end of six cycles of enzalutamide and EBRT treatment are considered successes.


Secondary Outcome Measures:
  • Health-related quality of life (HRQoL) measures [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Assessment of the effect of treatment on health-related quality of life including fatigue, sleep quality, as well as urinary, bowel, sexual and hormonal functioning.

  • Serum Hormone Levels [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Assessment of the effect of treatment on serum sex hormones including androgens and estrogens

  • Body Fat and Muscle Mass Measurements [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Assessment of the effect of treatment on body fat distribution and muscle mass.

  • Assessment of safety and tolerability according to adverse event reporting during the trial. [ Time Frame: 2 Years ] [ Designated as safety issue: Yes ]
    Assessment of safety and tolerability according to adverse event reporting during the trial.


Estimated Enrollment: 64
Study Start Date: January 2014
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide with External Beam Radiation
On this study patients will be treated with 6 months of Xtandi (enzalutamide). Approximately one-third of the way through this treatment they will receive EBRT. Starting on Day 1, all patients will ingest enzalutamide 160 mg/day at the same time each day without breaks (except as outlined for toxicity), with or without food, for 6 (28 day +/-3 days) cycles. Dose reduction of enzalutamide to 120 mg/day is allowed with the approval of the Medical Monitor. Patients will be instructed to return all unused capsules at each study visit to assess compliance and will receive study drug every 28 days (+/-3 days) for 6 cycles (24 weeks).
Drug: Enzalutamide
Other Name: Xtandi
Radiation: External Beam Radiation

Dose will be normalized such that exactly 98% of the PTV (planned target volume) receives the prescription dose and will be scored as per protocol. The maximum allowable dose within the PTV is 107% of the prescribed dose to a volume that is at least 0.03 cc. The minimum allowable dose within the PTV is >95% of the prescribed dose to a volume that is at least 0.03 cc.

EBRT shall receive prescription doses to the PTV 75.6- 79.2 Gy delivered in 1.8 Gy fractions.


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02028988

Contacts
Contact: Glenn Bubley, MD 617) 735-2062 gbubley@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Glenn Bubley, MD    617-635-2062    gbubley@bidmc.harvard.edu   
Contact: Mary-Ellen Morrissey, RN    617-635-2062    mmorris1@bidmc.harvard.edu   
Principal Investigator: Glenn Bubley, MD         
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Paul Nguyen, MD       PNGUYEN1@PARTNERS.ORG   
Contact: Andrew Hyatt       AHYATT@LROC.HARVARD.EDU   
Principal Investigator: Paul Nguyen, MD         
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Paul Nguyen, MD       PNGUYEN1@PARTNERS.ORG   
Contact: Andrew Hyatt       AHYATT@LROC.HARVARD.EDU   
Principal Investigator: Paul Nguyen, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Medivation, Inc.
Investigators
Principal Investigator: Glenn Bubley, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Glenn Bubley, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02028988     History of Changes
Other Study ID Numbers: 13-444
Study First Received: December 16, 2013
Last Updated: August 20, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Intermediate Risk Prostate Cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Site
Prostatic Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on November 24, 2014