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

• ClinicalTrials.gov Identifier: NCT02953860
• Recruitment Status: Completed
• First Posted: November 3, 2016
• Results First Posted: May 14, 2021
• Last Update Posted: May 14, 2021
• Sponsor: University of Colorado, Denver
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): University of Colorado, Denver

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Fulvestrant with Enzalutamide	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Fulvestrant Plus Enzalutamide in ER+/Her2- Advanced Breast Cancer
• Actual Study Start Date: July 6, 2017
• Actual Primary Completion Date: November 21, 2019
• Actual Study Completion Date: April 10, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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.	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.; Other Names: FASLODEX; MDV3100

Outcome Measures

Primary Outcome Measures :

1. Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant [ Time Frame: 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 :

1. Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) [ Time Frame: 24 Weeks ]
   The safety of the combination of enzalutamide with fulvestrant will be assessed according to CTCAE 4.03.
2. Percent Progression Free at 24 Weeks [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Colorado

University of Colorado

Aurora, Colorado, United States, 80045

Lone Tree Medical Center

Lone Tree, Colorado, United States, 80124

United States, Tennessee

West Cancer Center

Germantown, Tennessee, United States, 38138

Sponsors and Collaborators

University of Colorado, Denver

United States Department of Defense

Investigators

• Principal Investigator: Anthony D Elias, MD; University of Colorado, Denver

  Study Documents (Full-Text)

Documents provided by University of Colorado, Denver:

Study Protocol and Statistical Analysis Plan  [PDF] August 27, 2019

Informed Consent Form  [PDF] August 27, 2019

More Information

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02953860
• Other Study ID Numbers: 16-1001.cc
• First Posted: November 3, 2016
• Results First Posted: May 14, 2021
• Last Update Posted: May 14, 2021
• Last Verified: April 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Colorado, Denver:

Advanced Breast Cancer; ER+/Her2 Advanced Breast Cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Fulvestrant; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs