Breast Cancer
Conditions
Keywords
Advanced Breast Cancer, ER+/Her2 Advanced Breast Cancer
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.
Interventions
DRUGFulvestrant 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.
Sponsors
United States Department of Defense
University of Colorado, Denver
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 100 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Fulvestrant With Enzalutamide |
|---|---|
| Age, Continuous | 61 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 27 Participants |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 32 |
| other Total, other adverse events | 17 / 32 |
| serious Total, serious adverse events | 2 / 32 |
Outcome results
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.
Time frame: 24 Weeks
Population: All eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fulvestrant With Enzalutamide | Clinical Benefit Rate of the Combination of Enzalutamide/ Fulvestrant | 7 Participants |
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.
Time frame: 24 Weeks
Population: all eligible patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | fatigue | 17 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | vomiting | 9 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | constipation | 10 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | headache | 11 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | diarrhea | 7 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | cognitive dysfunction | 5 participants |
| Fulvestrant With Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Safety Profile) | nausea | 16 participants |
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.
Time frame: Up to 24 Weeks
Population: all eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fulvestrant With Enzalutamide | Percent Progression Free at 24 Weeks | 7 Participants |