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

NCT02091960 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 9785-CL-11212013-000093-29
• Study Type: interventional
• Target: 103
• Locations: 6 countries
• Sites: 39

Brief Summary

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.

Conditions

HER2 Amplified; Advanced Breast Cancer; Human Epidermal Growth Factor Receptor 2 (HER2)

Keywords

Enzalutamide; Trastuzumab; Breast cancer; HER2; Androgen receptor positive; Xtandi

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Overall Response Rate at Week 24

  24 weeks

• Best Overall Response Rate

  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

  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

  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

  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..

Study Arms (1)

Enzalutamide + Trastuzumab

EXPERIMENTAL

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; Drug: Trastuzumab

Interventions

Enzalutamide DRUG

Capsules for oral administration

Also known as: MDV3100, Xtandi

Enzalutamide + Trastuzumab

Trastuzumab DRUG

Intravenous infusion (IV) or subcutaneous injection if it is standard of care within a country

Also known as: Herceptin

Enzalutamide + Trastuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Medivation LLC, a wholly owned subsidiary of Pfizer Inc.: collaborator

Study Sites (39)

Site US10051

Anaheim, California, 92801, United States

Location

Site US10028

Los Angeles, California, 90048, United States

Location

Site US10035

San Francisco, California, 94115, United States

Location

Site US10079

Fort Myers, Florida, 33916, United States

Location

Site US10074

Gainesville, Florida, 32605, United States

Location

Site US10081

Chicago, Illinois, 60637, United States

Location

Site US10004

Indianapolis, Indiana, 46202, United States

Location

Site US10070

Boston, Massachusetts, 02215, United States

Location

Site US10078

St Louis, Missouri, 63110, United States

Location

Site US10072

Cincinnati, Ohio, 45242, United States

Location

Site US10048

Pittsburgh, Pennsylvania, 15213, United States

Location

Site US10029

Knoxville, Tennessee, 37909, United States

Location

Site US10042

Nashville, Tennessee, 37203, United States

Location

Site US10077

Nashville, Tennessee, 37232, United States

Location

Site US10076

Fort Worth, Texas, 76104, United States

Location

Site US10082

Houston, Texas, 77030, United States

Location

Site BE32003

Edegem, Antwerp, 2650, Belgium

Location

Site BE32013

Brasschaat, 2930, Belgium

Location

Site BE32016

Brussels, 1200, Belgium

Location

Site BE32001

Charleroi, 6000, Belgium

Location

Site BE32009

Leuven, 3000, Belgium

Location

Site BE32007

Liège, 4000, Belgium

Location

Site CA15022

Ottawa, Ontario, K1H 8L6, Canada

Location

Site CA15023

Toronto, Ontario, M4N 3M5, Canada

Location

Site CA15028

Regina, Saskatchewan, S4T7T1, Canada

Location

Site CA15026

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Site CA15001

Québec, G1S 4L8, Canada

Location

Site IT39005

Meldola, Forli, 47014, Italy

Location

Site IT39008

Lecce, 73100, Italy

Location

Site IT39003

Milan, 20132, Italy

Location

Site IT39002

Milan, 20141, Italy

Location

Site IT39001

Sondrio, 23100, Italy

Location

Site IT39021

Udine, 33100, Italy

Location

Site ES34014

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Site ES34010

Barcelona, 08035, Spain

Location

Site ES34013

Madrid, 28050, Spain

Location

Site GB44003

Edinburgh, EH4 2XU, United Kingdom

Location

Site GB44013

Manchester, M20 4BX, United Kingdom

Location

Site GB44001

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33591468 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Breast Neoplasms

Interventions

enzalutamide; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Clinical Transparency
• Organization: Astellas Global Development, Inc. (APGD)

astellas.resultsdisclosure@astellas.com

800-888-7704

Study Officials

• Executive Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 19, 2014
• Study Start: September 5, 2014
• Primary Completion: February 28, 2017
• Study Completion: January 30, 2024
• Last Updated: April 4, 2025
• Results First Posted: May 16, 2018

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

GB (3); BE (6); US (16); IT (6); ES (3); CA (5)