Status:
COMPLETED
ER Reactivation Therapy for Breast Cancer
Lead Sponsor:
Dartmouth-Hitchcock Medical Center
Conditions:
Metastatic Breast Cancer
Eligibility:
FEMALE
18+ years
Phase:
PHASE2
Brief Summary
Before anti-estrogens such as tamoxifen were developed to treat estrogen receptor (ER)-positive breast cancer, high-dose estrogen therapies were used. This seems counterintuitive since anti-estrogens ...
Detailed Description
Metastatic breast cancer is rarely cured by current therapies. ER+ breast cancers ultimately become resistant to all available anti-estrogens. Response rates to estrogens are similar to those of anti-...
Eligibility Criteria
Inclusion
- Women ≥18 years of age with clinical stage IV ER+/HER2- breast cancer, or with locally recurrent ER+/HER2- disease not amenable to therapy for curative intent.
- Patient must have been treated with an anti-estrogen at any time in their disease history. Combination regimens that include an anti-estrogen and any biologic, or targeted therapy, are permitted (e.g., any CDK inhibitor, everolimus, or any other novel biologics), and are considered to be a single hormonal therapy based regimen.
- Any number of prior lines of anti-estrogen (i.e., hormonal) therapy is permissible.
- One line of prior chemotherapy for advanced/metastatic disease is permissible.
- Histologic documentation of ER strongly+/HER2- breast cancer by core needle biopsy, fine needle aspiration, incisional biopsy, or surgical biopsy of ≥1 site(s) of metastatic or locally advanced disease performed as standard of care within the past 4 months for assessment of eligibility for study participation (except as noted below in c/d/e).
- ER strongly+ status defined as ER staining by immunohistochemistry in ≥50% of malignant cell nuclei with an intensity ≥2+ on a scale of 0-3+. These criteria are equivalent to an Allred score ≥6.
- HER2-negative status is defined as immunohistochemistry score of 0-1+, or with a FISH ratio of \<2 if IHC is 2+ or if IHC has not been done (as per ASCO/CAP definitions). In cases of borderline or equivocal HER2 status, eligibility will be determined by the PI.
- Archived tumor specimens: Excess tumor tissue must be available for research purposes. This will include tumor tissue sufficient to make ≥10 five-micron sections; more tumor tissue is preferred.
- Freshly acquired tumor specimens: As part of a clinically indicated biopsy procedure, an additional 1-3 cores or tissue fragments will be obtained by core needle or surgical biopsy for research purposes and FFPE.
- Patients with bone-only metastatic disease with a history of ER+/HER2- breast cancer are eligible, and bone biopsy is not required, providing their primary cancer is consistent with the above-described ER and HER2 criteria.
- Patients with non-bone metastatic disease in whom a safe and accurate biopsy of recurrent/metastatic disease cannot be readily obtained are also eligible, providing their primary cancer is consistent with the above-described ER and HER2 criteria.
- Patient must be a candidate for treatment with 17B-estradiol and an aromatase inhibitor.
- If the most recent therapy was in the adjuvant setting, the recurrence-free interval (time from initiation of adjuvant anti-estrogen therapy to clinical evidence of disease recurrence) must have been ≥2 years.
- If the most recent therapy was in the advanced/metastatic setting, the progression-free interval must have been ≥3 months (except in the case of investigational hormonal therapies).
- Patient must be post-menopausal based on either a history of an oophorectomy, or ≥1 year of amenorrhea. An elevated serum gonadotropin level and estradiol level in the postmenopausal range (as locally defined) can be used to confirm menopausal status in a subject with \<1 year of amenorrhea.
- Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
- Patient must be capable and willing to provide informed written consent for study participation.
- The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:
- Hematology panel
- hemoglobin \> 9 g/dL
- white blood cell (WBC) count (≥ 2,000/uL)
- platelet count ≥ 75,000/uL Serum biochemistry/metabolic panel
- creatinine ≤ 1.5 x upper limits of normal (ULN)
- total bilirubin ≤ 1.5 x upper limits of normal (ULN)
- ALT and AST ≤ 3.0 x upper limits of normal (ULN) For patients with liver metastasis: \< 5 x upper limits of normal (ULN)
Exclusion
- Treatment with fulvestrant within 16 weeks prior to study enrollment.
- Any other concurrent systemic anti-cancer treatments, including conventional chemotherapeutic agents and biological agents, during the study period.
- Anti-resorptive bone therapies (e.g., bisphosphonates, denosumab) are permitted.
- Any investigational cancer therapy in the last 3 weeks.
- Known CNS disease, unless clinically stable for ≥ 3 months.
- History of any of the following:
- deep venous thrombosis
- pulmonary embolism
- stroke
- acute myocardial infarction
- congestive heart failure
- previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%
Key Trial Info
Start Date :
March 11 2016
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 5 2024
Estimated Enrollment :
19 Patients enrolled
Trial Details
Trial ID
NCT02188745
Start Date
March 11 2016
End Date
July 5 2024
Last Update
July 17 2024
Active Locations (3)
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1
Baystate Medical Center
Springfield, Massachusetts, United States, 01199
2
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
3
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756