Preoperative Hormone Therapy for Postmenopausal Women With ER+ Clinical Stage T2-4 Tumors

Study Overview
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Brief Summary
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This phase II trial studies how well exemestane before surgery works in treating postmenopausal patients with newly diagnosed estrogen receptor positive stage II-III breast cancer. Estrogen can cause the growth of breast cancer cells. Hormone therapy using exemestane may fight breast cancer by blocking the use of estrogen by the tumor cells.

Detailed Description
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This study will develop preliminary data regarding the efficacy and safety of exemestane in the preoperative treatment of postmenopausal women with ER+ or PR+ tumors. This trial is also designed to develop a predictive model to correlate expression of the known isoforms of ER and progesterone receptor (PR) and the aromatase enzyme with response to estrogenic deprivation using exemestane.

Official Title
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Preoperative Hormone Therapy for Postmenopausal Women With ER+ Clinical Stage T2-4 Tumors. A Phase II Study to Identify Molecular Predictors for Hormone Responsiveness and/or Resistance.

Conditions
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Breast Cancer, Stage II Breast Cancer, Stage III Breast Cancer

Intervention / Treatment
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* Drug: Exemestane
* Drug: Exemestane and tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed breast cancer ER positive (+) Primary tumor 2-4 regional lymph nodes 0-2 (T2-4N0-2); patients may have metastatic disease, provided local-regional surgery is clinically indicated Clinical stage II/III Postmenopausal- defined as having had a previous bilateral oophorectomy or, for women with no prior hysterectomy, the absence of spontaneous menstrual cycles for more than 1 year Newly diagnosed Patients with prior non-breast malignancies are eligible if they have been disease free for >= 5 years before study entry; patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by surgery only, or lobular carcinoma in situ (LCIS) of the ipsilateral or contralateral breast that has been treated by surgery only are eligible, even if the cancer was diagnosed within 5 years before randomization Serum creatinine =< 1.5 x institutional upper limit of normal (ULN) Hemoglobin within normal limits for institution Absolute granulocyte count >= 1500 Platelet count >= 100,000 Serum glutamic oxaloacetic transaminase (SGOT), aspartate aminotransferase (AST) or serum glutamate pyruvate transaminase (SGPT), alanine aminotransferase (ALT) =< 2.5 x ULN Total bilirubin < 2 x ULN for institution Alkaline phosphatase < 2 x the ULN Exclusion Criteria: Completely resected Prior hormone or chemotherapy Unable to take oral medication Patients who have nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude their being subjected to protocol therapy

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Treatment (exemestane, surgery)<br>Patients receive exemestane orally daily for 4 months in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. | Drug: Exemestane<br>* Given PO<br>* Other names: PNU 155971;|
| Experimental: treatment (exemestane, tamoxifen, surgery)<br>Patients receive exemestane plus tamoxifen orally daily for 4 months in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. | Drug: Exemestane and tamoxifen<br>* exemestane 25 mg po daily and tamoxifen 20 mg po daily given concurrently for 4 months prior to surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate as Measured by Clinical Exam, Standard Imaging, and Surgical Pathology Findings | Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Evaluated using chi-square analysis. | Up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, Postmenopausal, Exemestane, Tamoxifen