Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Fulvestrant with Enzalutamide
Intervention description: 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 PO daily. Patients will receive a tumor biopsy at the start of treatment and 4 weeks after the start of treatment, with an optional 3rd biopsy at the end treatment.
Intervention MeSH terms: Fulvestrant
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: Female
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Advanced Breast Cancer; ER+/Her2 Advanced Breast Cancer

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. ER+ Her2- breast cancer

          2. Metastatic

          3. Female, at least 18 years of age

          4. Candidate for fulvestrant therapy - patients who have started fulvestrant may enter
             this trial if within 3 months of starting fulvestrant

          5. Measurable or evaluable by RECIST 1.1

          6. ECOG PS 0-2

          7. Able to swallow study drug and comply with study requirements

          8. Tumor available for fresh biopsy (two biopsies - pretreatment as regards enzalutamide,
             and during treatment at 4 weeks). The patient will be also be asked if they would be
             willing to provide a third biopsy at time of progression.

          9. If patient is pre- or peri- menopausal, then will need to have concurrent ovarian
             suppression. Patients may have already gotten the loading dose of ovarian suppression.
             Pre- or peri- menopausal subjects must have a negative urine pregnancy test confirmed
             at screening.

         10. ANC >1000/uL and platelets >75,000/uL at screening visit

         11. Total bilirubin < 1.5 times upper limit of normal (ULN) at the screening visit unless
             an alternate nonmalignant etiology exists (eg, Gilbert's disease)

         12. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 times ULN or <
             5 times ULN if patient has documented liver metastases

         13. Creatinine < 1.5 times ULN

         14. INR < 1.5 times ULN, or if on warfarin, can safely transition off for biopsy

         15. Willing to donate blood for research at 4 time points

         16. Written informed consent obtained prior to biopsies and blood samples

         17. Agreement to exercise appropriate use of contraception. Subjects should use 2
             acceptable methods of birth control (one of which must include a condom as a barrier
             method of contraception) starting at the time of screening for an enzalutamide study
             and continuing throughout the course of treatment and for at least three months after
             enzalutamide is discontinued.

        Exclusion Criteria:

          1. Current or previously treated brain or leptomeningeal metastases

          2. History of seizures

          3. Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide,
             enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464)

          4. Systemic estrogens or androgens within 14 days before initiating therapy. Vaginal
             estrogens are allowed if necessary for patient comfort.