Clinical trial NCT02953860: Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer
Official title: Phase II Trial of Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: Advanced Breast Cancer
ER+/Her2 Advanced Breast Cancer
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2016-11-03
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

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.

Primary outcomes:
measure: Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant
timeFrame: 24 Weeks
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (Safety Profile)
timeFrame: 24 Weeks
measure: Percent Progression Free at 24 Weeks
timeFrame: Up to 24 Weeks
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Lone Tree
country: United States
facility: Lone Tree Medical Center
state: Colorado
city: Germantown
country: United States
facility: West Cancer Center
state: Tennessee
Study officials:
affiliation: University of Colorado, Denver
name: Anthony D Elias, MD
role: PRINCIPAL_INVESTIGATOR
References: