Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Fulvestrant with Enzalutamide

• Registration Number: NCT02953860
• Lead Sponsor: University of Colorado, Denver

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.

Study Timeline

• Study First Submitted: 2016-11-01
• Study First Submitted QC: 2016-11-01
• Study First Posted: 2016-11-03
• Study Start: 2017-07-06
• Primary Completion: 2019-11-21
• Study Completion: 2020-04-10
• Results First Submitted: 2021-03-12
• Status Verified: 2021-04
• Results First Submitted QC: 2021-04-23
• Last Update Submitted: 2021-04-23
• Results First Posted: 2021-05-14
• Last Update Posted: 2021-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 32

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fulvestrant with Enzalutamide	Fulvestrant with Enzalutamide	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.

Primary Outcome Measures

Name	Time	Method
Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant	24 Weeks	To determine the clinical benefit rate at 24 weeks of the combination of enzalutamide/fulvestrant. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan or by caliper. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; clinical benefit rate (CBR) at 24 weeks (CR + PR + stable disease lasting at least 24 weeks.

Secondary Outcome Measures

Name	Time	Method
Percent Progression Free at 24 Weeks	Up to 24 Weeks	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. Percent (%) progression free at 24 weeks is the number of patients without disease progression after 24 weeks follow-up.
Number of Participants With Treatment-Emergent Adverse Events (Safety Profile)	24 Weeks	The safety of the combination of enzalutamide with fulvestrant will be assessed according to CTCAE 4.03.

Trial Locations

Locations (3)

Lone Tree Medical Center; 🇺🇸 Lone Tree, Colorado, United States

West Cancer Center; 🇺🇸 Germantown, Tennessee, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States