Phase 2 Study of Enzalutamide with Trastuzumab in Breast Cancer
Research type
Research Study
Full 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
IRAS ID
154760
Contact name
Stephen Chan
Contact email
Sponsor organisation
Astellas Pharma Global Development, Inc.
Eudract number
2013-000093-29
Clinicaltrials.gov Identifier
Research summary
This is a phase 2 study to assess the safety and effectiveness of Enzalutamide with Trastuzumab in Subjects with advanced breast cancer.
The purpose of this study is to learn how well enzalutamide works in patients who have metastatic or locally advanced breast cancer.
enzalutamide is currently approved by the United States Food and Drug Administration (FDA), Health Canada, and the European Commission for the treatment of men with prostate cancer.
Genes act as the blueprint and our cells are the factories for making all of the body’s proteins. Cell receptors are a type of protein that acts like locks on the surface of a cell that cause further chemical reactions inside of a cell. Sometimes in cancer, there are too many of these receptors compared to normal cells or these reactions happen more often than normal and lead to tumor cell growth. There are certain receptor proteins that play a role in breast cancer including HER2, the estrogen receptor (ER), and the progesterone receptor (PgR). If a patient has more of the receptor protein or has genes that are more active to produce the receptor protein, then they are noted as having HER2+, ER+, or PgR+ disease. The treatment for breast cancer depends on whether a patient is positive for these receptors so that a treatment that acts to stop the action of these proteins is chosen.
Another receptor, called the androgen receptor is also found in breast cancer tumors. Enzalutamide blocks the action of the androgen receptor (AR). Blocking the androgen receptor has been important in prostate cancer to delay tumors from growing.
Subject study participation is divided into three parts; Screening, Treatment and Long-term Follow-up. The total length of participation is dependent on how well subjects tolerate the drugs and/or how their disease progresses.
Approximately 80 subjects will take part in this study globally; approximately 40 in North America and 40 in Europe.LAY SUMMARY OF STUDY RESULTS:
This study was designed to evaluate the efficacy of enzalutamide with trastuzumab in
evaluable patients with HER2+ and AR+ metastatic or locally advanced breast cancer,
as measured by CBR (clinical benefit rate: the percentage of patients who have had
stable disease or have seen a positive response to treatment, for 6 or more months).
The CBR at 24 weeks was 23.6% (21 out of 89 patients) and median PFS
(Progression-free survival: the time from treatment to progression of the breast
cancer) was 3.4 months. The study met its primary endpoint on the pre-specified
minimum threshold of 10% for CBR (the main assessment point for the trial).
However, these results did not meet the prespecified proof of concept criteria (CBR 24
weeks > 40% and median PFS > 9 months); which is the evidence required to prove
that the treatment works better than current standard of care. Therefore, a decision
was made to discontinue development of enzalutamide in this indication.REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
14/WM/0156
Date of REC Opinion
19 Jun 2014
REC opinion
Further Information Favourable Opinion