Recruitment

Recruitment Status
Active, not recruiting
Estimated Enrollment
59

Inclusion Criteria

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.
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.
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.
...
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.
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.
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.
Patient must be capable and willing to provide informed written consent for study participation.
Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
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.
One line of prior chemotherapy for advanced/metastatic disease is permissible.
The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:
Any number of prior lines of anti-estrogen (i.e., hormonal) therapy is permissible.
Patient must be a candidate for treatment with 17B-estradiol and an aromatase inhibitor.
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.

Exclusion Criteria

congestive heart failure
Known CNS disease, unless clinically stable for ≥ 3 months.
Any investigational cancer therapy in the last 3 weeks.
...
congestive heart failure
Known CNS disease, unless clinically stable for ≥ 3 months.
Any investigational cancer therapy in the last 3 weeks.
Treatment with fulvestrant within 16 weeks prior to study enrollment.
stroke
pulmonary embolism
deep venous thrombosis
acute myocardial infarction
previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%

Summary

Conditions
Metastatic Breast Cancer
Type
Interventional
Phase
Phase 2
Design
  • Allocation: N/A
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Only females

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-estrogens in the metastatic setting. Given that ER+ breast cancers are often responsive to anti-estr...

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-estrogens in the metastatic setting. Given that ER+ breast cancers are often responsive to anti-estrogens and estrogens, alternating anti-estrogen/estrogen therapies may be more effective than continuous treatment with either type of agent. Anecdotal evidence indicates that such a strategy of alternating therapies is effective in some patients. Preclinical evidence suggests that anti-estrogen-resistant ER+ breast cancers are sensitized to the anti-tumor effects of estrogens. Such cells harbor subpopulations that can ultimately regain the ability to grow in the presence of estrogens, and revert to their anti-estrogen-sensitive state. The investigators will formally test whether alternating 17B-estradiol/anti-estrogen therapies is effective for the management of anti-estrogen-resistant metastatic ER+/HER2- breast cancer, and to identify molecular biomarkers that predict tumor response to 1) 17B-estradiol and 2) alternating 17B-estradiol/anti-estrogen therapies. If successful, this study would present a novel strategy to manage metastatic ER+/HER2- breast cancer by pre-emptively switching therapies prior to disease progression.

Inclusion Criteria

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.
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.
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.
...
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.
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.
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.
Patient must be capable and willing to provide informed written consent for study participation.
Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
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.
One line of prior chemotherapy for advanced/metastatic disease is permissible.
The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:
Any number of prior lines of anti-estrogen (i.e., hormonal) therapy is permissible.
Patient must be a candidate for treatment with 17B-estradiol and an aromatase inhibitor.
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.

Exclusion Criteria

congestive heart failure
Known CNS disease, unless clinically stable for ≥ 3 months.
Any investigational cancer therapy in the last 3 weeks.
...
congestive heart failure
Known CNS disease, unless clinically stable for ≥ 3 months.
Any investigational cancer therapy in the last 3 weeks.
Treatment with fulvestrant within 16 weeks prior to study enrollment.
stroke
pulmonary embolism
deep venous thrombosis
acute myocardial infarction
previous malignancy not treated with curative intent, or with an estimated recurrence risk ≥30%

Tracking Information

NCT #
NCT02188745
Collaborators
Not Provided
Investigators
  • Principal Investigator: Gary N Schwartz, MD Dartmouth-Hitchcock Medical Center
  • Gary N Schwartz, MD Dartmouth-Hitchcock Medical Center
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