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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Thomas Jefferson University
Sponsor:
Collaborators:
Astellas Pharma Inc
Medivation, Inc.
Information provided by (Responsible Party):
Thomas Jefferson University
ClinicalTrials.gov Identifier:
NCT02023463
First received: December 23, 2013
Last updated: May 29, 2014
Last verified: May 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Thomas Jefferson University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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:
  • Change in PSA levels [ Time Frame: Baseline up to 6 months ] [ Designated as safety issue: No ]
    Evaluated using linear mixed models. Mixed models will make use of all available data, and can estimate individual levels of change.

  • Quality of life (QoL), measured using the EPIC, AUA symptom index, and the PROMIS Fatigue Scale [ Time Frame: Baseline up to 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 24
Study Start Date: April 2014
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders 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
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: NCT02023463

Contacts
Contact: Robert Den, MD Robert.Den@jeffersonhospital.org
Contact: Radiation Oncology Protocol Office 215-955-8619

Locations
United States, Pennsylvania
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Robert Den, MD         
Contact: Radiation Oncology Protocol Office    215-955-8619      
Principal Investigator: Robert Den, MD         
Sub-Investigator: Leonard Gomella, MD         
Sub-Investigator: Karen Knudsen, PhD         
Sub-Investigator: William Kevin Kelly, DO         
Sub-Investigator: Costas Lallas, MD         
Sub-Investigator: Edouard Trabulsi, MD         
Sub-Investigator: Jianqing Lin, MD         
Sub-Investigator: Jean Hoffman-Censits, MD         
Sub-Investigator: Adam Dicker, MD, PhD         
Sub-Investigator: Mark Hurwitz, MD         
Sub-Investigator: Ruth Birbe, MD         
Sub-Investigator: Peter McCue, MD         
Sub-Investigator: Perry Weiner, MD         
Sponsors and Collaborators
Thomas Jefferson University
Astellas Pharma Inc
Medivation, Inc.
Investigators
Principal Investigator: Robert Den, MD Thomas Jefferson University
  More Information

Additional Information:
No publications provided

Responsible Party: Thomas Jefferson University
ClinicalTrials.gov Identifier: NCT02023463     History of Changes
Other Study ID Numbers: 13P.461, 2013-027
Study First Received: December 23, 2013
Last Updated: May 29, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Carcinoma
Genital Diseases, Male
Genital Neoplasms, Male
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Prostatic Diseases
Urogenital Neoplasms
Goserelin
Leuprolide
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Fertility Agents
Fertility Agents, Female
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 23, 2014