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

Breast Cancer Clinical Trial

Official title:

Phase II Trial of Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02953860
• Other study ID #: 16-1001.cc
• Status: Completed
• Phase: Phase 2
• Start date: July 6, 2017
• Est. completion date: April 10, 2020

Study information

• Verified date: April 2021
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: April 10, 2020
• Est. primary completion date: November 21, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• 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 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.

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	West Cancer Center	Germantown	Tennessee
United States	Lone Tree Medical Center	Lone Tree	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	United States Department of Defense

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant	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.	24 Weeks
Secondary	Number of Participants With Treatment-Emergent Adverse Events (Safety Profile)	The safety of the combination of enzalutamide with fulvestrant will be assessed according to CTCAE 4.03.	24 Weeks
Secondary	Percent Progression Free at 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.	Up to 24 Weeks