Recruitment

Recruitment Status
Recruiting
Estimated Enrollment
59

Inclusion Criterias

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.
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.
Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
...
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.
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.
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.
Patient must be capable and willing to provide informed written consent for study participation.
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.
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.
One line of prior chemotherapy for advanced/metastatic disease is permissible.
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.
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.
The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:

Exclusion Criterias

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

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 Criterias

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.
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.
Baseline radiographic staging, including specifically either PET/CT, or CT (CAP) and bone scan.
...
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.
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.
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.
Patient must be capable and willing to provide informed written consent for study participation.
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.
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.
One line of prior chemotherapy for advanced/metastatic disease is permissible.
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.
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.
The following laboratory values must be confirmed for eligibility within 28 days prior to initiation of study therapy:

Exclusion Criterias

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

Locations

Springfield, Massachusetts, 01199
Rochester, Minnesota, 55905
Lebanon, New Hampshire, 03756
Springfield, Massachusetts, 01199
Rochester, Minnesota, 55905
Lebanon, New Hampshire, 03756

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