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

• ClinicalTrials.gov Identifier: NCT02023463
• Recruitment Status: Active, not recruiting
• First Posted: December 30, 2013
• Last Update Posted: December 9, 2020
• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University
• Collaborators: Astellas Pharma Inc; Medivation, Inc.
• Information provided by (Responsible Party): Thomas Jefferson University ( Sidney Kimmel Cancer Center at Thomas Jefferson University )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer	Drug: Enzalutamide; Drug: Goserelin acetate; Drug: Leuprolide acetate; Radiation: Radiation therapy	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase Ib Trial of Enzalutamide in Combination With Radiation Therapy and LHRH Agonist Therapy in the Management of Intermediate and High-Risk Prostate Cancer
• Actual Study Start Date: April 2, 2014
• Actual Primary Completion Date: July 10, 2017
• Estimated Study Completion Date: January 1, 2040

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Acute toxicities, monitored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 criteria [ Time Frame: Up to 1 month post completion of enzalutamide ]
   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.

Secondary Outcome Measures :

1. Change in PSA levels [ Time Frame: Baseline up to 6 months ]
   Evaluated using linear mixed models. Mixed models will make use of all available data, and can estimate individual levels of change.
2. Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale [ Time Frame: Baseline up to 1 year ]
   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.

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Sidney Kimmel Cancer Center at Thomas Jefferson University

Astellas Pharma Inc

Medivation, Inc.

Investigators

• Principal Investigator: Robert Den, MD; Thomas Jefferson University

More Information

Additional Information:

Kimmel Cancer Center at Thomas Jefferson University, an NCI-Designated Cancer Center 

Thomas Jefferson University Hospitals 

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT02023463
• Other Study ID Numbers: 13P.461; 2013-027 ( Other Identifier: CCRRC )
• First Posted: December 30, 2013
• Last Update Posted: December 9, 2020
• Last Verified: December 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Leuprolide; Goserelin; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents