Safety Study of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Medivation, Inc.
Sponsor:
Collaborator:
Astellas Pharma Inc
Information provided by (Responsible Party):
Medivation, Inc.
ClinicalTrials.gov Identifier:
NCT02007512
First received: December 3, 2013
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to determine if enzalutamide given in combination with exemestane is safe and effective in patients with advanced breast cancer.


Condition Intervention Phase
Breast Cancer
Drug: Enzalutamide
Drug: exemestane
Drug: Placebo (for enzalutamide)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Efficacy and Safety of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer That Is Estrogen or Progesterone Receptor-Positive and HER2-Normal

Resource links provided by NLM:


Further study details as provided by Medivation, Inc.:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    To determine the benefit of exemestane plus enzalutamide versus exemestane plus placebo as assessed by progression-free survival (PFS) in patients with advanced breast cancer that is estrogen or progesterone receptor-positive or both (ER+/PgR+) and human epidermal growth factor receptor 2 (HER2)-normal


Secondary Outcome Measures:
  • Clinical Benefit Rate [ Time Frame: 24 Months ] [ Designated as safety issue: No ]

    Clinical benefit rate, defined as the proportion of patients with a best response of complete response(CR), partial response (PR), or of stable disease (SD) lasting ≥ 24 weeks;

    • Best objective response rate;
    • Duration of response;
    • Time to response;
    • Time to progression;
    • PFS rate at 6 months.

  • Pharmacokinetics [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Cmax for enzalutamide and exemestane one hour pre dose and exemestane 6 hours post dose at specified study visits.


Other Outcome Measures:
  • Health-related Quality of Life [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    Assessments of health-related quality of life will be performed using the European Organization for Research and Treatment of Cancer (EORTC) quality-of-life core questionnaire (QLQ-C30) and breast cancer module(QLQ-BR23) at specified intervals and at time of disease progression.

  • Androgen Receptor (AR) Expression by Immunohistochemistry (IHC) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    To determine the percent of androgen receptor (AR) nuclear expression and signaling in breast tissue and to evaluate the relationship of this expression with enzalutamide effects on circulating tumor biomarkers, circulating hormones, and clinical outcomes.


Estimated Enrollment: 240
Study Start Date: November 2013
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enzalutamide & exemestane
Enzalutamide 160 mg/day administered as four 40-mg soft gelatin capsules by mouth once daily with or without food and exemestane 50mg tablet once daily after food.
Drug: Enzalutamide
160 mg/day administered as four 40-mg soft gelatin capsules by mouth once daily with or without food.
Other Names:
  • MDV3100
  • XTANDI
Drug: exemestane
25 mg or 50 mg tablet administered as a single capsule by mouth once daily after food.
Active Comparator: placebo & exemestane
placebo and exemestane 25 mg once daily after food.
Drug: exemestane
25 mg or 50 mg tablet administered as a single capsule by mouth once daily after food.
Drug: Placebo (for enzalutamide)
Sugar pill manufactured to mimic enzalutamide administered as four soft gelatin capsules by mouth once daily with or without food.

Detailed Description:

This is a Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Efficacy and Safety of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer That Is Estrogen or Progesterone Receptor-Positive and HER2-Normal.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing and able to provide informed consent;
  • Postmenopausal;
  • Advanced histologically confirmed breast cancer that is ER+, PgR+, or both, and HER-2 normal;
  • Up to one prior hormone therapy and up to one prior chemotherapy in the advanced setting is allowed;
  • Availability of a representative, formalin-fixed, paraffin-embedded tumor specimen that enabled the diagnosis of breast cancer with viable tumor cells in a tissue block or unstained serial slides accompanied bay an associated pathology report;
  • Measurable disease. Patients with non-measurable bone or skin disease as their only manifestation of advanced breast cancer are also eligible;
  • ECOG status of 0 or 1;

Exclusion Criteria:

  • Any severe concurrent disease, infection, or comorbid condition that renders the patient inappropriate for enrollment in the opinion of the investigator;
  • Any condition or reason that interferes with the patient's ability to participate in the trial, that may cause undue risk, or complicates the interpretation of safety data, in the opinion of the investigator;
  • Current or previously treated brain metastasis or leptomeningeal disease;
  • Prior therapy (> 28 days) with exemestane in the metastatic setting (Patients receiving exemestane in the adjuvant setting and having disease recurrence more than 1 year after treatment discontinuation are eligible);
  • Requires treatment for tuberculosis or HIV infection;
  • Radiation therapy within 7 days before randomization;
  • History of another invasive cancer within 5 years before randomization;
  • History of seizure or any condition that may predispose to seizure;
  • Clinically significant cardiovascular disease;
  • Active gastrointestinal disorder;
  • Major surgery within 28 days prior to randomization;
  • Treatment with any oral anticancer or with any non-hormonal anticancer agent within 14 days before randomization;
  • Treatment with any approved or investigational agent that blocks androgen synthesis or targets the androgen receptor;
  • Treatments with any of the following medications within 14 days before randomization: Estrogens, Androgens, or Systemic radionuclides;
  • Hypersensitivity reaction to exemestane.
  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: NCT02007512

Contacts
Contact: Jane Dennison 855-349-1891 breastcancertrials@medivation.com
Contact: Amy Grekowicz, MPH (415) 543-3470 mdv3100_12@medivation.com

  Show 26 Study Locations
Sponsors and Collaborators
Medivation, Inc.
Astellas Pharma Inc
  More Information

No publications provided

Responsible Party: Medivation, Inc.
ClinicalTrials.gov Identifier: NCT02007512     History of Changes
Other Study ID Numbers: MDV3100-12
Study First Received: December 3, 2013
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Medivation, Inc.:
advanced breast cancer
enzalutamide
MDV3100
Estrogen receptor positive
Progesterone receptor positive
HER-2 normal

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Estrogens
Progesterone
Exemestane
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Progestins
Antineoplastic Agents
Therapeutic Uses
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 26, 2014