Enzalutamide, Radiation Therapy and Hormone Therapy in Treating Patients With Intermediate or High-Risk Prostate Cancer

Phase Ib Trial of Enzalutamide in Combination With Radiation Therapy and LHRH Agonist Therapy in the Management of Intermediate and High-Risk Prostate Cancer

This phase I trial studies the side effects and best way to give enzalutamide, radiation therapy, and hormone therapy in treating patients with intermediate or high-risk prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as enzalutamide, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. Giving enzalutamide, radiation therapy, and hormone therapy may be an effective treatment for prostate cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Recurrent Prostate Cancer; Stage III Prostate Cancer; Adenocarcinoma of the Prostate; Stage IV Prostate Cancer; Stage IIB Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: Goserelin acetate; Drug: Leuprolide acetate; Radiation: Radiation therapy

Detailed Description

PRIMARY OBJECTIVE:

1) To assess the safety of the combination of neoadjuvant and concurrent enzalutamide with an luteinizing-hormone-releasing hormone (LHRH) agonist and radiation therapy.

SECONDARY OBJECTIVES:

1. To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using prostate specific antigen (PSA) kinetics.
2. To determine the efficacy of the combination of enzalutamide with an LHRH agonist and radiation therapy using PSA nadir.
3. To describe patient-reported outcomes including: Expanded Prostate Cancer Index Composite (EPIC), American Urological Association (AUA) Symptom Index, PROstate magnetic resonance (MR) Imaging Study (PROMIS) Fatigue Scale.

OUTLINE:

Patients receive enzalutamide orally (PO) once daily (QD) for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate subcutaneously (SC) or leuprolide acetate intramuscularly (IM) or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH agonist therapy, patients undergo either intensity modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT) daily five days a week for 8 weeks.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Prostate adenocarcinoma without distant metastatic disease with either Gleason score ≥ 7, PSA ≥ 10 ng/ml, or T2b or greater disease
2. Age > 18
3. Performance Status: ECOG 0-1

4. Hematologic (minimal values):

   • Absolute neutrophil count > 1,500/mm3
   • Hemoglobin > 8.0 g/dl
   • Platelet count > 100,000/mm3

5. Hepatic function

   • Total bilirubin < Upper limit of normal (ULN)(except for Gilbert's disease)
   • AST (SGOT) < 1.5 x ULN
   • ALT (SGPT) < 1.5 x ULN
6. Creatinine < 1.5 x ULN
7. Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

Exclusion Criteria:

1. Patients with a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, brain arteriovenous malformation or the use of concomitant medications that may lower the seizure threshold
2. History of urological surgery or procedures predisposing to GU complications after radiation (will be determined by radiation oncologist)
3. History of diverticulitis, rectal bleeding or other lower GI diseases predisposing to GI complications after radiation (will be determined by radiation oncologist)
4. History of prior chemotherapy or pelvic irradiation,
5. History of prior invasive malignant cancer(s) within the last 5 years except adequately treated or controlled basal cell or squamous cell carcinoma of the skin.
6. Documented distant metastatic disease. NOTE: pelvic lymphadenopathy is NOT excluded.
7. Prior radical prostatectomy or cryosurgery for prostate cancer or bilateral orchiectomy.
8. No experimental medications within 30 days of study entry

9. Patients currently taking the following medications:

   • CYP2C8 inhibitors (e.g. Gemfibrozil)
   • CYP2C8 inducers (e.g. rifampin)
   • CYP3A4 inhibitors (itraconazole)
   • CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)

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

Experimental: Treatment (enzalutamide, radiation therapy, hormone therapy); Patients receive enzalutamide PO QD for 6 months. Beginning 2 weeks after start of enzalutamide, patients receive LHRH agonist therapy with goserelin acetate SC or leuprolide acetate IM or SC for 6 months (intermediate risk patients) or 24 months (high risk patients) post-radiation therapy. Beginning 8 weeks after the start of LHRH therapy, patients undergo either IMRT or VMAT daily five days a week for 8 weeks.

Drug: Enzalutamide; Given PO; Other Names: Xtandi; MDV3100; Drug: Goserelin acetate; Given SC; Other Names: Zoladex; Goserelin; Drug: Leuprolide acetate; Given IM or SC; Other Names: Leuprorelin; Leuprolide; Radiation: Radiation therapy; Undergo image-guided radiation therapy; Other Names: irradiation; radiation; radiotherapy; therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria	An exact 2-sided binomial 90% confidence interval will be computed and reported. Toxicity will be monitored and if there is greater than 10% incidence of grade 3 or higher gastrointestinal (GI)/genitourinary (GU)/fatigue lasting more than 7 days despite optimal treatment, the trial will be re-evaluated.	Up to 1 month post completion of enzalutamide

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in PSA levels	Evaluated using linear mixed models. Mixed models will make use of all available data, and can estimate individual levels of change.	Baseline up to 6 months
Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale	QoL measures will also be assessed via linear mixed models, as an exploratory evaluation of potential clinical correlates, such as age, race, stage, Gleason score, etc.	Baseline up to 1 year

Collaborators and Investigators

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Astellas Pharma Inc; Medivation, Inc.
• Investigators: Principal Investigator: Robert Den, MD, Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospitals

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2014
• Primary Completion (Actual): July 10, 2017
• Study Completion (Estimated): January 1, 2040

Study Registration Dates

• First Submitted: December 23, 2013
• First Submitted That Met QC Criteria: December 23, 2013
• First Posted (Estimated): December 30, 2013

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 6, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Leuprolide; Goserelin
• Other Study ID Numbers: 13P.461; 2013-027 (Other Identifier: CCRRC)

Drug and device information, study documents

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