Clinical Trials /

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

NCT02007512

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety Study of Enzalutamide in Combination With Exemestane in Patients With Advanced Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: MDV3100-12
  • SECONDARY ID: 2013-002717-35
  • SECONDARY ID: C3431008
  • NCT ID: NCT02007512

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EnzalutamideMDV3100, XTANDIEnzalutamide & exemestane
exemestaneplacebo & exemestane
Placebo (for enzalutamide)placebo & exemestane
exemestaneEnzalutamide & exemestane

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Enzalutamide & exemestaneExperimentalEnzalutamide 160 mg/day administered as four 40-mg soft gelatin capsules by mouth once daily with or without food and exemestane 50mg capsule once daily after food.
  • Enzalutamide
  • exemestane
placebo & exemestaneActive Comparatorplacebo and exemestane 25 mg once daily after food.
  • exemestane
  • Placebo (for enzalutamide)

Eligibility 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;

          -  Eastern Cooperative Oncology Group (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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS): Intent-to-Treat (ITT) Population
Time Frame:From randomization until PD, last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Safety Issue:
Description:PFS was defined as the time in months from randomization to the first documentation of progression of disease (PD) or death on study due to any cause, whichever occurred first. PD according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1) was defined as greater than or equal to (>=) 20 percent (%) increase in the sum of diameters of the target lesions taking as a reference the smallest sum recorded since the start of treatment or unequivocal progression in non-target lesions or the appearance of 1 or more new lesions. The analysis of PFS was based on investigator assessment of disease progression. Participants who were not known to have had a PFS event at the analysis date were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.

Secondary Outcome Measures

Measure:Clinical Benefit Rate-24 (CBR-24)
Time Frame:From randomization up to 3 years
Safety Issue:
Description:CBR-24: Percentage of participants with a best response of complete response (CR), partial response (PR), or stable disease (SD) sustained for atleast 24 weeks, as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. SD: Neither sufficient reduction to qualify as PR nor sufficient increase to qualify as PD, using the smallest sum diameters during study as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions.
Measure:Best Objective Response Rate
Time Frame:From randomization until CR or PR, whichever occurred first (up to 3 years)
Safety Issue:
Description:Best objective response rate: Percentage of participants with measurable disease and with a best response of CR or PR according to RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: Atleast 30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. Response evaluation was based on investigators' judgment.
Measure:Duration of Objective Response
Time Frame:From first documentation of CR or PR until PD, or last tumor assessment without PD before new antitumor treatment initiation or death due to any cause, whichever occurred first (up to 3 years)
Safety Issue:
Description:Duration of objective response: Time from first documentation of CR or PR, to the first documentation of PD or death due to any cause, whichever occurred first as determined by investigator using RECIST 1.1. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants with no PD or death (after initial CR or PR) at the analysis date were censored at last tumor assessment date prior to date of new antitumor treatment or data cutoff.
Measure:Time to Response
Time Frame:From randomization until first documentation of CR or PR, or last tumor assessment without PD or death prior to new antitumor treatment initiation, whichever occurred first (up to 3 years)
Safety Issue:
Description:Time to response: Time from randomization to first documentation of CR or PR. CR: Disappearance of all (target and non-target) lesions and normalization of tumor marker level for non-target lesions. All lymph nodes (target and non-target) must be non-pathological in size (<10 mm short axis). PR: >=30% decrease in sum of diameters of target lesions, using baseline sum diameters as reference. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who were not known to have had a CR or PR were censored at last tumor assessment date prior to data cutoff or date of new treatment initiation, whichever occurred first.
Measure:Time to Progression
Time Frame:From randomization until PD or last tumor assessment without PD before new antitumor treatment initiation, whichever occurred first (up to 3 years)
Safety Issue:
Description:Time to progression was defined as the time from the date of randomization to PD defined by the investigator using RECIST 1.1. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. Participants who did not experience disease progression, time to progression was right censored at the date of the last tumor assessment prior to data cutoff or date of new antitumor treatment, whichever occurred first.
Measure:Progression Free Survival (PFS) at 6 Months
Time Frame:Month 6
Safety Issue:
Description:PFS at 6 months was defined as the percentage of participants with no event of disease progression at Month 6 landmark, estimated by Kaplan-Meier methods. PFS was defined as the time in months from randomization to the first documentation of PD or death on study due to any cause, whichever occurred first. PD: >=20% increase (an absolute increase of >=5 mm) in sum of diameters of target lesions, using the smallest sum during the study as a reference (including baseline sum), or unequivocal progression of existing non-target lesions, or appearance of atleast 1 new target or non-target lesions. The analysis of PFS was based on investigator assessment of disease progression.
Measure:Concentration Versus Time Summary of Enzalutamide
Time Frame:Predose on Day 29, 57 and 113
Safety Issue:
Description:Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.
Measure:Concentration Versus Time Summary of Exemestane
Time Frame:Predose, 1 and 6 hour postdose on Day 29, 57, 113 and 169
Safety Issue:
Description:Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.
Measure:Concentration Versus Time Summary of N-desmethyl Enzalutamide
Time Frame:Predose on Day 29, 57 and 113
Safety Issue:
Description:N-desmethyl enzalutamide was the active metabolite of enzalutamide. Concentration versus time summary was calculated by setting concentration values below limit of quantitation to zero.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • advanced breast cancer
  • enzalutamide
  • MDV3100
  • Estrogen receptor positive (ER +)
  • Progesterone receptor positive (PgR +)
  • HER-2 normal

Last Updated

January 10, 2018