Enzalutamide and Hormone Therapy Before, During, and After Radiation for High Risk Localized Prostate Cancer

Phase 2 Study of Enzalutamide and GnRH Agonist Before, During and After Radiation Therapy in Treatment of Patients With High-risk Localized Prostate Cancer

The study is being done to find out whether combining two FDA approved drugs along with radiation therapy for the treatment of high risk localized prostate cancer is safe and well tolerated.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: Leuprolide acetate; Radiation: radiation

Detailed Description

• this pilot study will assess the safety and tolerability of combining enzalutamide with an gonadotropin-releasing hormone agonist (GnRH) and external beam radiation
• Correlative imaging and tissue biopsy analysis will be performed to assess the radiographic response to enzalutamide plus gonadotropin-releasing hormone agonist (GnRH) therapy as well as intratumoral androgen signaling

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• histologically proven adenocarcinoma of the prostate within 6 months of screening
• Eastern Cooperative Oncology Group(ECOG) score 0-2
• adequate organ and and blood marrow function
• must be a candidate for long-term androgen deprivation in combination with external beam radiation for the treatment of high risk prostate cancer
• patient must permit a targeted prostate biopsy at the time of study initiation or at the beginning of radiation treatment
• men who are sexually active with female partners of child-bearing potential mush agree to use adequate contraception

Exclusion Criteria:

• prior treatment with agents known to have endocrine effects on prostate cancer
• treatment with corticosteroids within 4 weeks of enrollment
• treatment with androgens within 6 months of enrollment
• may not be receiving any other investigational agents
• Prostate specific antigen greater than 160ng/dL
• history of malignancy( other than non-melanoma skin cancer) within 5 years
• uncontrolled intercurrent illness
• cardiovascular event within 6 months of enrollment
• seizure or seizure disorder history
• contraindications to MRI- pacemakers, clips, etc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Enzalutamide, Leuprolide, radiation; Single arm Enzalutamide 160 mg daily for 6 months Leuprolide acetate 22.5mg every 3 months or 45mg every 6 months Radiation therapy as standard of care	Drug: Enzalutamide; 160mg by mouth each day; Other Names: Xtandi; Drug: Leuprolide acetate; 22.5 mg intramuscular every 3 months or 45mg intramuscular every 6 months; Other Names: Lupron; Radiation: radiation; External beam radiation will be delivered as per standard radiation therapy protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety, as Measured by the Number of Patients With at Least One Adverse Event as Assess by NCI Common Terminology Criteria for Adverse Events (CTCAE) vs. 40 When Combining Enzalutamide With a GnRH and External Beam Radiation	Assessment will number of participants who experience adverse events greater than or equal to Grade 3, as defined by NCI Common terminology criteria for adverse events(CTCAE) v4.0	12 months following initiation of treatment with enzalutamide plus GnRH agonist

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fold Change in Intra-tumoral Androgen Regulated Gene Expression Pre and Post Combination Therapy	Fold change of Intra-tumoral Androgen Regulated Gene Expression (PSA, FKBP5, TMPRSS2, and NDRG1) will be measure at 12 months post therapy.	12 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Astellas Pharma US, Inc.
• Investigators: Principal Investigator: Kevin D Courtney, MD, PhD, UT Southwestern Medical Center

Publications and helpful links

General Publications

• Li J, Alyamani M, Zhang A, Chang KH, Berk M, Li Z, Zhu Z, Petro M, Magi-Galluzzi C, Taplin ME, Garcia JA, Courtney K, Klein EA, Sharifi N. Aberrant corticosteroid metabolism in tumor cells enables GR takeover in enzalutamide resistant prostate cancer. Elife. 2017 Feb 13;6:e20183. doi: 10.7554/eLife.20183.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): June 9, 2018
• Study Completion (Actual): June 9, 2018

Study Registration Dates

• First Submitted: February 10, 2014
• First Submitted That Met QC Criteria: February 14, 2014
• First Posted (Estimate): February 17, 2014

Study Record Updates

• Last Update Posted (Actual): October 12, 2020
• Last Update Submitted That Met QC Criteria: September 17, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: prostate cancer, enzalutamide, radiation, hormone therapy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide
• Other Study ID Numbers: STU 082013-032

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No