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A Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2 Positive (HER2+), Androgen Receptor Positive (AR+) Metastatic or Locally Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02091960
Recruitment Status : Active, not recruiting
First Posted : March 19, 2014
Results First Posted : May 16, 2018
Last Update Posted : April 6, 2020
Sponsor:
Collaborator:
Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE March 18, 2014
First Posted Date  ICMJE March 19, 2014
Results First Submitted Date  ICMJE February 27, 2018
Results First Posted Date  ICMJE May 16, 2018
Last Update Posted Date April 6, 2020
Actual Study Start Date  ICMJE August 28, 2014
Actual Primary Completion Date February 28, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
Clinical Benefit Rate (CBR) [ Time Frame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days. ]
Clinical benefit rate was defined as the percentage of evaluable participants with best objective response of confirmed complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, or prolonged stable disease (≥ 24 weeks). Complete response (CR) was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis. Partial response (PR) was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions, with persistence of non-target lesions and no new lesions. Stable disease (SD) was defined as < 30% decrease and < 20% increase in the size of target lesions, persistence of non-target lesions, and no new lesions. PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date that PR or CR was first observed. SD required confirmation with equivalent or improved assessment no less than 8 weeks after enrollment.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
Clinical Benefit Rate (CBR) [ Time Frame: up to 2 years ]
Defined as proportion of evaluable subjects with best objective response of complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
  • Overall Response Rate at Week 24 [ Time Frame: 24 weeks ]
    Overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) per RECIST 1.1. Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis. Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persistence of non-target lesions and no new lesions. PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date of scan that PR or CR was first observed.
  • Best Overall Response Rate [ Time Frame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days. ]
    Best overall response was the best response across all time points, based on investigator assessments. Best overall response rate was defined as the percentage of evaluable participants with a best objective response of confirmed complete response (CR) or partial response (PR) at any time during the study per RECIST 1.1. Complete response was defined as the disappearance of all target and non-target lesions and no new lesions, and lymph nodes all < 10 mm in short axis. Partial response was defined as disappearance of target lesions or a ≥ 30% decrease in the size of target lesions with persistence of non-target lesions and no new lesions. PR and CR required confirmation with equivalent or improved assessment no less than 4 weeks after the date of scan that PR or CR was first observed.
  • Progression-free Survival [ Time Frame: From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days. ]
    Progression-free survival was defined as the time from the date of first dose of enzalutamide until the date of disease progression per RECIST 1.1, or death from any cause on study, whichever occurred first. Participants who initiated another antitumor therapy before documented progressive disease (PD) or death, or who progressed or died after missing 2 or more consecutive radiological assessments were censored at the date of the last radiological assessment showing no progression. Progressive disease was defined as a ≥ 20% increase in the size of target lesions and at least a 5 mm increase in size of target lesions from smallest size on study, or unequivocal progression of non-target lesions, or any new lesions.
  • Time to Progression [ Time Frame: From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days. ]
    Time to progression was defined as the time from the first date of enzalutamide treatment until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, who progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.
  • Duration of Response [ Time Frame: Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression, initiation of new therapy or withdrawal of consent. The median duration of treatment was 70 days, and the maximum was 660 days. ]
    Duration of response was defined as the time from the date of first documentation of response (CR or PR) until the date of disease progression per RECIST 1.1. Participants who initiated another anti-tumor therapy before documented PD, progressed after missing two or more consecutive radiological assessments or who died before disease progression were censored at the date of the last radiological assessment showing no progression.
  • Time to Response [ Time Frame: From the date of first dose of study drug to the data cut-off date of 28 February 2017; the median duration of treatment was 70 days, and the maximum was 660 days. ]
    Time to response was defined as the time from the first date of enzalutamide treatment to initial CR or PR and was calculated for participants with a CR or PR.
  • Number of Participants With Adverse Events (AEs) [ Time Frame: From the first dose date of study drug to 30 days after the last dose date of study drug or the start of subsequent treatment or date of death, whichever was first; median duration of treatment was 70 days, and the maximum was 660 days. ]
    An AE was defined as any untoward medical occurrence in a patient administered study drug or who underwent study procedures and did not necessarily have a causal relationship with treatment. An abnormality identified during a medical test was defined as an AE only if the abnormality induced clinical signs or symptoms, required active intervention, required interruption or discontinuation of study medication, or was clinically significant in the opinion of the investigator. An AE was defined as serious if it resulted in any of the following outcomes:
    • Death
    • Was life-threatening
    • Persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions
    • Congenital anomaly, or birth defect
    • Inpatient hospitalization or prolongation of hospitalization
    • Other medically important event. Drug-related AEs were those assessed by the investigator as AEs whose relationship to the to the study drugs could not be ruled out.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2014)
  • Overall response rate (CR+PR) according to RECIST 1.1 criteria [ Time Frame: 24 weeks ]
  • Best overall response rate according to RECIST 1.1 criteria [ Time Frame: 24 weeks ]
  • Progression free survival [ Time Frame: up to 2 years ]
    Defined as the time from the date of first dose of enzalutamide (Study Day 1) until the date of disease progression per RECIST 1.1, or death from any cause on study, whichever occurs first
  • Time to progression [ Time Frame: up to 2 years ]
    Defined as the time from the first date of enzalutamide treatment until the date of disease progression per RECIST 1.1
  • Duration of response [ Time Frame: up to 2 years ]
    Defined as the time from the date of first documentation of response (CR or PR) until the date of disease progression
  • Time to Response [ Time Frame: up to 2 years ]
    Defined as the time from the first date of enzalutamide treatment to initial CR or PR
  • Safety assessed by physical examinations, vital signs, laboratory assessments, electrocardiograms, left ventricular ejection fraction (LVEF) by echocardiogram or multi-gated acquisition scan (MUGA), and evaluation of adverse events [ Time Frame: up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Patients With Human Epidermal Growth Factor Receptor 2 Positive (HER2+), Androgen Receptor Positive (AR+) Metastatic or Locally Advanced Breast Cancer
Official Title  ICMJE A Phase 2, Multicenter, Open-label Study to Assess the Efficacy and Safety of Enzalutamide With Trastuzumab in Subjects With HER2+ AR+ Metastatic or Locally Advanced Breast Cancer
Brief Summary The purpose of this study is to evaluate the efficacy of enzalutamide with trastuzumab in patients with HER2+ AR+ metastatic or locally advanced breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • HER2 Amplified
  • Advanced Breast Cancer
  • Human Epidermal Growth Factor Receptor 2 (HER2)
Intervention  ICMJE
  • Drug: Enzalutamide
    Capsules for oral administration
    Other Names:
    • MDV3100
    • Xtandi
  • Drug: Trastuzumab
    Intravenous infusion (IV) or subcutaneous injection if it is standard of care within a country
    Other Name: Herceptin
Study Arms  ICMJE Experimental: Enzalutamide + Trastuzumab
Participants received 160 mg enzalutamide orally once daily and 6 mg/kg trastuzumab administered by intravenous infusion or subcutaneous injection every 21 days. Participants continued on treatment until disease progression, unacceptable toxicity or any other discontinuation criteria were met.
Interventions:
  • Drug: Enzalutamide
  • Drug: Trastuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 22, 2017)
103
Original Estimated Enrollment  ICMJE
 (submitted: March 18, 2014)
80
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date February 28, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The subject has histologically or cytologically proven adenocarcinoma of the breast that is HER2+
  • The subject has AR+ breast cancer
  • The subject has metastatic disease or has locally advanced disease that is not amendable to curative treatment
  • The subject has measurable disease or nonmeasurable, evaluable disease per RECIST 1.1. (NOTE: pleural effusions, ascites or other third fluid space are not evaluable diseases per RECIST 1.1).
  • The subject has received at least 1 line of therapy in the metastatic or locally advanced disease setting. The subject has been documented to have progressed by determination of the investigator on a regimen containing an anti-HER2 agent as the most recent regimen or the most recent anti-HER2 regimen was discontinued for any toxicity, with the exception of a cardiotoxicity.
  • The subject has adequately recovered from toxicities due to prior therapy.
  • The subject has an Eastern Cooperative Oncology Group performance (ECOG) status ≤ 1 at Screening and Day 1
  • The subject has available at the site a representative, formalin-fixed, paraffin-embedded, tumor specimen that enabled the definitive diagnosis of breast cancer with adequate viable tumor cells in a tissue block (preferred) or ≥ 10 (20 preferred) freshly cut, unstained, serial slides and the associated pathology report

Exclusion Criteria:

  • The subject has a severe concurrent disease, infection, or comorbidity that would make the subject inappropriate for enrollment.
  • The subject has current or previously treated brain metastasis or active leptomeningeal disease. Brain imaging is required during screening in all subjects to exclude the presence of unequivocal central nervous system disease.
  • The subject has a history of a non-breast cancer malignancy with the following exceptions:

    • The subject with a previous history of a non-invasive carcinoma is eligible if he/she has had successful curative treatment any time prior to Screening.
    • For all other malignancies, the subject is eligible if they have undergone potentially curative therapy and they have been considered disease free for at least 5 years prior to Screening.
  • The subject has a history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke, significant brain trauma).
  • The subject has a history of loss of consciousness, cerebrovascular accident, or transient ischemic attack within 12 months before the Day 1 visit.
  • The subject has had a hypoglycemic episode requiring medical intervention while on insulin (or other anti-diabetic) treatment within 12 months before Day 1.
  • The subject had a major surgical procedure, substantial open biopsy, or significant traumatic experience within 28 days before the Day 1 visit, or anticipation of need for major surgical procedure during the course of the study.
  • The subject has had palliative radiation therapy to bone metastases within 14 days prior to the Day 1 visit (side effects from radiation must be resolved).
  • The subject has received chemotherapy, immunotherapy, or any other systemic anticancer therapy, with the exception of anti-HER2 therapy (e.g., trastuzumab), within 14 days prior to the Day 1 visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02091960
Other Study ID Numbers  ICMJE 9785-CL-1121
2013-000093-29 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
Investigators  ICMJE
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP