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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

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ClinicalTrials.gov Identifier: NCT02091960
Recruitment Status : Active, not recruiting
First Posted : March 19, 2014
Results First Posted : May 16, 2018
Last Update Posted : August 29, 2018
Sponsor:
Collaborator:
Medivation, Inc.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

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.

Condition or disease Intervention/treatment Phase
HER2 Amplified Advanced Breast Cancer Human Epidermal Growth Factor Receptor 2 (HER2) Drug: Enzalutamide Drug: Trastuzumab Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 103 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : August 28, 2014
Actual Primary Completion Date : February 28, 2017
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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.
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




Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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.


  2. 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.


  3. 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.


  4. 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.

  5. 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.

  6. 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.

  7. 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.



Information from the National Library of Medicine

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02091960


  Show 38 Study Locations
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Medivation, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
  Study Documents (Full-Text)

Documents provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Statistical Analysis Plan  [PDF] March 23, 2017
Study Protocol  [PDF] April 17, 2017


Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02091960     History of Changes
Other Study ID Numbers: 9785-CL-1121
2013-000093-29 ( EudraCT Number )
First Posted: March 19, 2014    Key Record Dates
Results First Posted: May 16, 2018
Last Update Posted: August 29, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
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/

Studies a U.S. FDA-regulated Drug Product: Yes

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Enzalutamide
Trastuzumab
Breast cancer
HER2
Androgen receptor positive
Xtandi

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Androgens
Antineoplastic Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs