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

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

The purpose of this study was to evaluate the efficacy of enzalutamide with trastuzumab in patients with HER2+ AR+ metastatic or locally advanced breast cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Breast Cancer; HER2 Amplified; Human Epidermal Growth Factor Receptor 2 (HER2)
• Intervention / Treatment: Drug: Enzalutamide; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brasschaat, Belgium, 2930
    • Site BE32013
  • Bruxelles, Belgium, 1200
    • Site BE32016
  • Charleroi, Belgium, 6000
    • Site BE32001
  • Leuven, Belgium, 3000
    • Site BE32009
  • Liege, Belgium, 4000
    • Site BE32007
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Site BE32003
• Canada
  • Quebec, Canada, G1S 4L8
    • Site CA15001
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Site CA15022
    • Toronto, Ontario, Canada, M4N 3M5
      • Site CA15023
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T7T1
      • Site CA15028
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Site CA15026
• Italy
  • Lecce, Italy, 73100
    • Site IT39008
  • Milan, Italy, 20132
    • Site IT39003
  • Milano, Italy, 20141
    • Site IT39002
  • Sondrio, Italy, 23100
    • Site IT39001
  • Udine, Italy, 33100
    • Site IT39021
  • Forli
    • Meldola, Forli, Italy, 47014
      • Site IT39005
• Spain
  • Barcelona, Spain, 08035
    • Site ES34010
  • Madrid, Spain, 28050
    • Site ES34013
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Site ES34014
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • Site GB44003
  • Manchester, United Kingdom, M20 4BX
    • Site GB44013
  • Nottingham, United Kingdom, NG5 1PB
    • Site GB44001
• United States
  • California
    • Anaheim, California, United States, 92801
      • Site US10051
    • Los Angeles, California, United States, 90048
      • Site US10028
    • San Francisco, California, United States, 94115
      • Site US10035
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Site US10079
    • Gainesville, Florida, United States, 32605
      • Site US10074
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Site US10081
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site US10004
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Site US10070
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site US10078
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Site US10072
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Site US10048
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Site US10029
    • Nashville, Tennessee, United States, 37203
      • Site US10042
    • Nashville, Tennessee, United States, 37232
      • Site US10077
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Site US10076
    • Houston, Texas, United States, 77030
      • Site US10082

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: Xtandi; MDV3100; Drug: Trastuzumab; Intravenous infusion (IV) or subcutaneous injection if it is standard of care within a country; Other Names: Herceptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate (CBR)	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.	Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate at Week 24	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.	24 weeks
Best Overall Response Rate	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.	Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
Progression-free Survival	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.	From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
Time to Progression	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.	From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
Duration of Response	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.	Tumor assessments were performed every 8 weeks through week 49, and then every 12 weeks thereafter until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days..
Time to Response	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.	From the date of first dose of study drug until disease progression or death; the median duration of treatment was 70 days, and the maximum was 660 days.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a participant administered study drug/who underwent study procedures and did not necessarily have a causal relationship with treatment. Abnormalities identified during medical tests were defined as an AE if they induced clinical signs/symptoms, required active intervention, interruption or discontinuation of study medication, or were clinically significant to the investigator. An AE was defined as serious if any of the following resulted: Death, was life-threatening, persistent or significant disability/incapacity or substantial disruption of ability to conduct normal life functions, congenital anomaly/ birth defect, inpatient hospitalization/prolongation of hospitalization or other medically important event. TEAE was defined as an AE observed during the treatment emergent period, which is from first dose date of study drug to 30 days after last dose date or the start of subsequent treatment or date of death, whichever is first.	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 (Up to 3031 days)

Collaborators and Investigators

• Sponsor: Astellas Pharma Global Development, Inc.
• Collaborators: Medivation LLC, a wholly owned subsidiary of Pfizer Inc.
• Investigators: Study Director: Executive Medical Director, Astellas Pharma Global Development, Inc.

Publications and helpful links

General Publications

• Wardley A, Cortes J, Provencher L, Miller K, Chien AJ, Rugo HS, Steinberg J, Sugg J, Tudor IC, Huizing M, Young R, Abramson V, Bose R, Hart L, Chan S, Cameron D, Wright GS, Graas MP, Neven P, Rocca A, Russo S, Krop IE. The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. Breast Cancer Res Treat. 2021 May;187(1):155-165. doi: 10.1007/s10549-021-06109-7. Epub 2021 Feb 16.

Helpful Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2014
• Primary Completion (Actual): February 28, 2017
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 18, 2014
• First Posted (Estimated): March 19, 2014

Study Record Updates

• Last Update Posted (Actual): April 4, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: HER2; Breast cancer; Xtandi; Enzalutamide; Trastuzumab; Androgen receptor positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Trastuzumab
• Other Study ID Numbers: 9785-CL-1121; 2013-000093-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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 products 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. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No