Enzalutamide + External Beam Rt For Prostate

NCT02028988 | Completed Phase 2 Results DMC

• 1 other identifier: 13-444
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

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.

Conditions

Intermediate Risk Prostate Cancer

Keywords

Intermediate Risk Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With PSA at or Below 0.2 ng/ml

  Percentage of participants with PSA level of less than or equal to 0.2 ng/ml at the end of six cycles of enzalutamide and EBRT treatment. Post-treatment PSA nadir level has been shown to be a validated intermediate cancer endpoint in similar settings. The chosen cut-off of 0.2 ng/ml was informed by D'Amico et al Lancet Oncology 2012. PSA levels determined through established methods (blood draw and serum analysis).

  End of treatment, up to 27 weeks.

Secondary Outcomes (22)

• Median DHEA-S

  Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

• Median Androstenedione

  Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

• Median Testosterone

  Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

• Median Free Testosterone

  Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

• Median Estrone

  Assessed cycle 1, cycle 5, and end of treatment, up to 27 weeks

Study Arms (1)

Enzalutamide with External Beam Radiation

EXPERIMENTAL

Enzalutamide 40 mg orally 4x daily for 6 (28 day +/-3 days) cycles. External Beam Radiation Therapy (EBRT) - 7-10 weeks after beginning Enzalutamide 75.6 to 79.2 Gy in 1.8 Gy fractions for up to 11 weeks. \*Patients that are unable to complete enzalutamide therapy will still be treated with EBRT

Drug: Enzalutamide; Radiation: External Beam Radiation

Interventions

Enzalutamide DRUG

Also known as: Xtandi

Enzalutamide with External Beam Radiation

External Beam Radiation RADIATION

Enzalutamide with External Beam Radiation

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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%;

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Medivation, Inc.: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Related Publications (1)

• 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.

  PMID: 33636278 RESULT

MeSH Terms

Interventions

enzalutamide

Results Point of Contact

• Title: Glenn Bubley MD
• Organization: Dana-Farber Cancer Institute

gbubley@bidmc.harvard.edu

617-735-2062

Study Officials

• Glenn Bubley, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: January 7, 2014
• Study Start: February 1, 2014
• Primary Completion: October 1, 2017
• Study Completion: January 1, 2018
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)