Estrogen in Postmenopausal Women With ER Positive Metastatic Breast Cancer After Failure of Sequential Endocrine Therapy

Study Overview
=================
Brief Summary
-----------------
This trial seeks to confirm the response rate for estrace treatment in a patients with hormone receptor positive metastatic breast cancer heavily pre-treated with modern endocrine therapies.

Detailed Description
-----------------
Prior to the current standard of care utilizing estrogen deprivation or antiestrogen therapy to treat hormonally sensitive breast cancers, treatment with pharmacologic doses of estrogen was a common technique used to treat post-menopausal women with hormone sensitive metastatic disease that resulted in durable responses with regression of disease. A randomized trial comparing tamoxifen and pharmacologic doses of estrogen demonstrated similar rates of response with long-term follow-up data confirming a survival benefit for those treated with the estrogen preparation. Additional data has shown that post-menopausal women with hormonally sensitive tumors that have progressed on prior endocrine therapies responded to treatment with pharmacologic doses of estrogen. These data, coupled with pre-clinical data that postmenopausal levels of estrogen can be used to cause apoptosis (programmed cell death within the tumor) and tumor regression in exhaustively treated endocrine resistant disease form the rationale for the proposed clinical trial. This trial seeks to confirm the response rate for estrace treatment in a patient population heavily pre-treated with modern endocrine therapies.

Official Title
-----------------
A Single Arm Phase II Study of Pharmacologic Dose Estrogen in Postmenopausal Women With Hormone Receptor-Positive Metastatic Breast Cancer After Failure of Sequential Endocrine Therapies

Conditions
-----------------
Breast Cancer, Cancer of the Breast, Neoplasms, Breast

Intervention / Treatment
-----------------
* Drug: Estrace
* Drug: Anastrozole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed estrogen and/or progesterone receptor-positive breast cancer metastatic breast cancer Clinically determined evaluable disease Post-menopausal woman Previous clinical benefit from prior anti-estrogen therapies and subsequent failure of at least 2 prior endocrine therapies. May have had chemotherapy for adjuvant &/or metastatic disease. May have had radiation therapy but not to the only site of disease. Ecog performance status </= 2. Life expectancy of > 6 months Exclusion Criteria: Chemotherapy or radiotherapy within 1 week of beginning treatment in the clinical trial Brain metastasis Prior history of or active thrombophlebitis, deep venous thrombosis or pulmonary embolus Current vaginal bleeding Hypercalcemia or hypocalcemia History of or active hepatic adenoma No other malignancies within the past 5 years with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Estrace & Anastrozole<br>Estrace 10 mg three times a day for 3 months. After 3 months of estrace, the estrace will be stopped and anastrazole 1 mg daily will be administered | Drug: Estrace<br>* Estrace 10 mg three times daily will be administered for 3 months.<br>Drug: Anastrozole<br>* After 3 months of estrace, patients who do not have evidence of disease progression will then be switched to received Anastrozole 1 mg daily as long as their disease benefits from this treatment<br>* Other names: Arimidex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival is defined as the time from assignment of treatment to the time of disease progression or death from any cause | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Response rate was defined per RECIST version 1.0. In this study, response rate was defined as including patients with either a complete response (complete disappearance of all target lesions with changes confirmed by repeat assessments performed no less than 4 weeks after the criteria for response was first met) or a partial response (at least 30% decrease in the sum of the longest diameter of the target lesions) | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Breast cancer, Metastatic breast cancer, ER positive breast cancer, Hormonal therapy