Breast Cancer
Conditions
Keywords
ER+/Her2 - breast cancer, Preoperative Fulvestrant, Enzalutamide
Brief summary
This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after \ 4 months on treatment.
Detailed description
This is a randomized two arm phase II study to further evaluate the efficacy of fulvestrant plus enza compared to single agent fulvestrant in postmenopausal women with locally advanced AR+/ER+/Her2- BC who will have local surgery after \ 4 months on treatment. After consent, all patients will get a tissue biopsy, and than half the patients will get fulvestrant alone (standard dosing) and the other half of the patients will get fulvestrant plus enzalutamide. At \ 4 weeks, a biopsy will be done and therapy will be continued. Hormone therapy will continue for \ 4 months at which point the patients will undergo surgical resection.
Interventions
DRUGEnzalutamide
160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
DRUGFulvestrant
500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Sponsors
University of Colorado, Denver
United States Department of Defense
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 101 Years
Healthy volunteers
No
Inclusion criteria
* ER+ Her2- breast cancer * Stage at least T2 or greater * Planned to get local surgery * Postmenopausal, or if pre- or peri- menopausal, then will need to have concurrent ovarian suppression. * At least 18 years of age * Not on anticoagulants * PS 0-2 * Able to swallow study drug and comply with study requirements * ANC \>1000/uL, platelets \>75,000/uL at screening visit * Total bilirubin \< 1.5 times upper limit of normal (ULN) at the screening visit unless an alternate nonmalignant etiology exists (eg, Gilbert's disease) * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 times ULN or \< 5 times ULN if patient has documented liver metastases * Creatinine \< 1.5 times ULN * INR \< 1.5 times ULN, or if on warfarin, can safely transition off for biopsy * Willing to donate blood for research at 4 time points * Willing to undergo core biopsies for research at study entry and at \~4 weeks. * Willing to donate tissue to research from the surgical specimen * Written informed consent obtained prior to biopsies and blood samples
Exclusion criteria
* Current or previously treated brain or leptomeningeal metastases * History of seizures * Prior treatment with an anti-androgen (abiraterone, ARN-509, bicalutamide, enzalutamide, ODM-201, TAK-448, TAK-683, TAK-700, VT-464). * 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 |
|---|---|---|
| Number of Patients With a PEPI Score Equal to Zero at Post Treatment | 16 Weeks | The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence. PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and \>= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | 15 months | Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately. |
| Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate | 4 years | To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects. |
| Androgen Receptor (AR) Expression | 16 Weeks | The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAnthony D Elias, MD
University of Colorado, Denver
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fulvestrant Without Enzalutamide 500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
Fulvestrant: 500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC) | 27 |
| Fulvestrant With Enzalutamide 500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC), plus160mg of Enzalutamide will be given daily.
Enzalutamide: 160mg of Enzalutamide will be given daily in conjunction with Fulvestrant.
Fulvestrant: 500mg Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC) | 34 |
| Total | 61 |
Baseline characteristics
| Characteristic | Fulvestrant Without Enzalutamide | Fulvestrant With Enzalutamide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 15 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 19 Participants | 37 Participants |
| Age, Continuous | 59.3 years STANDARD_DEVIATION 13.08 | 61.47 years STANDARD_DEVIATION 10.1 | 60.49 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 27 Participants | 32 Participants | 59 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 22 Participants | 24 Participants | 46 Participants |
| Region of Enrollment United States | 27 participants | 34 participants | 61 participants |
| Sex: Female, Male Female | 27 Participants | 34 Participants | 61 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 27 | 0 / 34 |
| other Total, other adverse events | 26 / 27 | 34 / 34 |
| serious Total, serious adverse events | 1 / 27 | 3 / 34 |
Outcome results
Primary
Number of Patients With a PEPI Score Equal to Zero at Post Treatment
The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy. It is a model that combines estrogen receptor (ER) level, pathologic tumor site, nodal status, and Ki67 score at the time of surgery to predict subsequent risk of cancer recurrence. PEPI scoring is typically discretized into three risk groups: 0 (low risk of recurrence and best outcome), 1-3 (intermediate risk), and \>= 4 (high risk). This study was concerned only with the distinction between zero and non-zero PEPI scores. Zero is the minimum score, and there is no maximum score. Lower scores are better.
Time frame: 16 Weeks
Population: 59 patients were evaluable. One patient was unable to participate in treatment after baseline and the other came off study for treatment change.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Fulvestrant Without Enzalutamide | Number of Patients With a PEPI Score Equal to Zero at Post Treatment | 2 Participants |
| Fulvestrant With Enzalutamide | Number of Patients With a PEPI Score Equal to Zero at Post Treatment | 8 Participants |
Secondary
Androgen Receptor (AR) Expression
The strength of AR signaling was measured by the percentage of downstream AR-regulated genes that were expressed.
Time frame: 16 Weeks
Population: The number of evaluable patients for this outcome measure is 49 because these were the patients who had available lab data for AR%.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant Without Enzalutamide | Androgen Receptor (AR) Expression | 85 percentage of genes expressed |
| Fulvestrant With Enzalutamide | Androgen Receptor (AR) Expression | 80 percentage of genes expressed |
Secondary
Correlation Between PEPI Score and Disease-free Survival, Clinical Benefit Rate, and Overall Response Rate
To assess the association between PEPI score and the clinical, outcomes such as DFS, ORR, clinical benefit for all subjects.
Time frame: 4 years
Secondary
Disease-free Survival
Disease-free survival is defined as the time in months from the start of fulvestrant until documented disease progression or death. Complete and partial response for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
Time frame: 15 months
Population: 59 patients were evaluable. One patient was unable to participate in treatment after baseline and the other came off study for treatment change.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fulvestrant Without Enzalutamide | Disease-free Survival | 3.6 months |
| Fulvestrant With Enzalutamide | Disease-free Survival | 3.7 months |