Description:
A phase 2 study to evaluate the tolerability and clinical activity of adding enzalutamide to fulvestrant treatment in women with advanced breast cancer that are ER and/or PR positive and Her2 normal.
A phase 2 study to evaluate the tolerability and clinical activity of adding enzalutamide to fulvestrant treatment in women with advanced breast cancer that are ER and/or PR positive and Her2 normal.
Active, not recruiting
Phase 2
Drug | Synonyms | Arms |
---|---|---|
Fulvestrant with Enzalutamide | FASLODEX, MDV3100 | Fulvestrant with Enzalutamide |
A phase 2 study to evaluate the tolerability and clinical activity of adding enzalutamide to fulvestrant treatment in women with advanced breast cancer that are ER and/or PR positive and Her2 normal.
This is a single arm, non-randomized, open-label phase 2 study designed to evaluate the tolerability and clinical activity of adding enzalutamide to fulvestrant treatment in women with advanced breast cancer that are ER and/or PR-positive and Her2 normal. In this study 500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC) and 160mg of Enzalutamide will be, in conjunction with Fulvestrant, PO daily.
Name | Type | Description | Interventions |
---|---|---|---|
Fulvestrant with Enzalutamide | Experimental | 500mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC) and 160mg of Enzalutamide will be given, in conjunction with Fulvestrant, PO daily. |
|
Inclusion Criteria:
- ER+ Her2- breast cancer
- Metastatic
- At least 18 years of age
- Candidate for fulvestrant therapy - patients who have started fulvestrant may enter this trial if within 3 months of starting fulvestrant
- Measurable or Evaluable by RECIST 1.1
- PS 0-2
- Able to swallow study drug and comply with study requirements
- Tumor available for fresh biopsy (two biopsies - pretreatment as regards enzalutamide, and during treatment @4 weeks). (The patient will be asked if they would be willing to provide a third biopsy at time of progression)
- Patients may already have gotten the loading doses of fulvestrant and/or ovarian suppression
- If patient is pre- or peri- menopausal, then will need to have concurrent ovarian suppression.
- ANC >1000/uL, platelets >75,000/uL at screening visit
- Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or < 5 times ULN if patient has documented liver metastases
- Creatinine < 1.5 times ULN
- INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy
- Willing to donate blood for research at 4 time points
- Written informed consent obtained prior to biopsies and blood samples
Exclusion Criteria:
- Current or previously treated brain or leptomeningeal metastases
- History of seizures
- Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464).
- Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal estrogens are allowed if necessary for patient comfort.
Maximum Eligible Age: | 101 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Measure: | Clinical benefit rate of the combination of enzalutamide/ fulvestrant |
Time Frame: | 24 Weeks |
Safety Issue: | |
Description: | Clinical benefit rate |
Measure: | Androgen receptor (AR) expression in breast tissue in the tumor biopsies of each patient |
Time Frame: | 24 Weeks |
Safety Issue: | |
Description: | Patient biopsies will be obtained pretreatment, during treatment, and at the time of tumor progression to determine the AR expression and signaling in the breast tissue. The degree of AR expression in the nucleus will be reported by immunohistochemistry (IHC) strength of staining (0-3+) and % nuclei stained and the relationship between tumor response and degree of AR expression and/or AR signaling will be examined |
Measure: | Progression-free survival (PFS) |
Time Frame: | 24 Weeks |
Safety Issue: | |
Description: | PFS is defined as the time from the first day of enzalutamide treatment (Study Day 1) until documented disease progression or death on study, whichever occurs first. |
Measure: | Overall response rate |
Time Frame: | 24 Weeks |
Safety Issue: | |
Description: |
Measure: | AR signaling in breast cancer tissue in the tumor biopsies |
Time Frame: | 24 weeks |
Safety Issue: | |
Description: |
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Anthony Elias |
December 20, 2016