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

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT02953860
• Collaborator: United States Department of Defense (U.S. Fed)
• Enrollment: 32
• Locations: 3
• Arm: 1
• Actual Duration (Months): 33.1
• Patients Per Site: 10.7
• Patients Per Site Per Month: 0.3

Study Details

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
• 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: Jul 6, 2017
• Actual Primary Completion Date: Nov 21, 2019
• Actual Study Completion Date: Apr 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 [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) [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 [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

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	University of Colorado	Aurora	Colorado	United States	80045
2	Lone Tree Medical Center	Lone Tree	Colorado	United States	80124
3	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)

• Study Protocol and Statistical Analysis Plan - Aug 27, 2019
• Informed Consent Form - Aug 27, 2019

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT02953860
• Other Study ID Numbers: 16-1001.cc
• First Posted: Nov 3, 2016
• Last Update Posted: May 14, 2021
• Last Verified: Apr 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• 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; Fulvestrant

Study Results

Participant Flow

Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
Period Title: Overall Study
STARTED	32
COMPLETED	32
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 3.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 9.4%
White	27 84.4%
More than one race	1 3.1%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	32 100%

Outcome Measures

1. Primary Outcome

Title	Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant
Description	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.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

All eligible patients

Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
Measure Participants	32
Count of Participants [Participants]	7 21.9%

2. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (Safety Profile)
Description	The safety of the combination of enzalutamide with fulvestrant will be assessed according to CTCAE 4.03.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

all eligible patients

Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
Measure Participants	32
fatigue	17 53.1%
nausea	16 50%
vomiting	9 28.1%
constipation	10 31.3%
headache	11 34.4%
diarrhea	7 21.9%
cognitive dysfunction	5 15.6%

3. Secondary Outcome

Title	Percent Progression Free at 24 Weeks
Description	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.
Time Frame	Up to 24 Weeks

Outcome Measure Data

Analysis Population Description

all eligible patients

Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
Measure Participants	32
Count of Participants [Participants]	7 21.9%

Adverse Events

Time Frame	AEs collected during treatment (which lasted up to a year)
Adverse Event Reporting Description	CTCAE 4.0 Collected with each monthly visit, patients kept diary.
Arm/Group Title	Fulvestrant With Enzalutamide
Arm/Group 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, in conjunction with Fulvestrant, PO daily. 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.
All Cause Mortality
	Fulvestrant With Enzalutamide
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Serious Adverse Events
	Fulvestrant With Enzalutamide
	Affected / at Risk (%)	# Events
Total	2/32 (6.3%)
Cardiac disorders
myocardial infarction	1/32 (3.1%)	1
Hepatobiliary disorders
cholecystitis	1/32 (3.1%)	1
Other (Not Including Serious) Adverse Events
	Fulvestrant With Enzalutamide
	Affected / at Risk (%)	# Events
Total	17/32 (53.1%)
Endocrine disorders
Hot Flashes	6/32 (18.8%)	6
Gastrointestinal disorders
nausea	16/32 (50%)	16
vomiting	9/32 (28.1%)	9
constipation	10/32 (31.3%)	10
anorexia	9/32 (28.1%)	9
General disorders
Fatigue	17/32 (53.1%)	17
Musculoskeletal and connective tissue disorders
achiness	14/32 (43.8%)	14
Nervous system disorders
insomnia	6/32 (18.8%)	6
headache	11/32 (34.4%)	11
cognitive dysfunction	5/32 (15.6%)	5

Limitations/Caveats

limited size of trial not randomized heavily pretreated somewhat heterogeneous population

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.