Clinical Trials /

Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

NCT02955394

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer
  • Official Title: Randomized Phase II Trial of Preoperative Fulvestrant With or Without Enzalutamide in ER+/Her2- Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 16-1042.cc
  • NCT ID: NCT02955394

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
EnzalutamideMDV3100Fulvestrant With Enzalutamide
FulvestrantFASLODEXFulvestrant Without Enzalutamide

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Fulvestrant Without EnzalutamidePlacebo Comparator500 mg of Fulvestrant will be given IM on days 1, 15, 28, then every 4 weeks as per standard of care (SOC)
  • Fulvestrant
Fulvestrant With EnzalutamideExperimental500 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
  • Fulvestrant

Eligibility Criteria

        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.
      
Maximum Eligible Age:101 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Document the number of patients in both treatment arms separately who have a PEPI score equal to 0 at post treatment
Time Frame:16 Weeks
Safety Issue:
Description:The preoperative endocrine prognostic index (PEPI) is a validated measure of pathologic response to endocrine therapy.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:16 Weeks
Safety Issue:
Description:To determine the percentage of progression-free survival (PFS) (complete and partial response plus stable disease) for the single drug arm and combination of enzalutamide/fulvestrant arm separately.
Measure:Correlate PEPI score and Progression-free survival, Clinical Benefit Rate, and Overall Response Rate
Time Frame:16 Weeks
Safety Issue:
Description:To assess the association between PEPI score and the clinical, outcomes such as PFS, ORR, clinical benefit for all subjects.
Measure:Androgen Receptor (AR) expression
Time Frame:16 Weeks
Safety Issue:
Description:Nuclear AR expression and AR pathway expression correlation with clinical outcomes. AR expression is associated with resistance to anti-estrogen therapy. Its blockade may enhance response.
Measure:Clinical Benefit Rate
Time Frame:16 weeks
Safety Issue:
Description:To determine the percentage of clinical benefit rate (complete and partial response plus stable disease) for the single drug arm and combination of enzalutamide/fulvestrant arm separately.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • ER+/Her2 - breast cancer
  • Preoperative Fulvestrant
  • Enzalutamide

Last Updated

October 13, 2017