Treatment and Survival Continuation Study of Atamestane Plus Toremifene vs Letrozole in Advanced Breast Cancer

Study Overview
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Brief Summary
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Protocol 777-CLP-32 is the treatment and survival continuation protocol of Biomed 777-CLP-29, and will continue to compare combined hormonal therapy using the experimental aromatase inhibitor (AI) atamestane combined with the FDA-approved anti-estrogen toremifene (Fareston®), to the single agent FDA-approved aromatase inhibitor letrozole (Femara®) for the treatment of advanced breast cancer. The purpose of this study is to determine whether maximal estrogen suppression achieved via the combination of atamestane, plus toremifene (Fareston®), is more effective than letrozole (Femara®) in delaying the growth of breast cancer.

Detailed Description
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Aromatase is an enzyme expressed in tissues such as muscle and fat in postmenopausal women. These non-ovarian tissues become the dominant sources of estrogen in postmenopausal women. Breast cancer cells are often very dependent on estrogens to continue to grow. Atamestane blocks the formation of estrogens from androgenic precursors in the body via the aromatase enzyme. Toremifene blocks circulating and intracellular estrogens from stimulating estrogen receptors in breast cancer cells. The goal of therapy with atamestane, an aromatase inhibitor, in combination with the estrogen receptor antagonist, toremifene, is to achieve complete suppression of estrogen stimulation of breast cancer cells. This study is designed to determine whether combined hormonal therapy will lengthen the time to disease progression and the survival time for subjects with advanced breast cancer.

Official Title
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Open Label Treatment and Survival Continuation Study of Atamestane Plus Toremifene Versus Letrozole in Advanced Breast Cancer

Conditions
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Breast Neoplasms, Neoplasms, Hormone-Dependent

Intervention / Treatment
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* Drug: Atamestane
* Drug: toremifene
* Drug: letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible to receive continued treatment, subjects must remain eligible to receive study drug at the time of their last Biomed 777-CLP-29 visit To continue on survival follow-up, subjects must be in survival follow-up in study Biomed 777-CLP-29 Written informed consent obtained for subjects who continue study drug treatment Exclusion Criteria: Subjects who have withdrawn consent to participate in Biomed 777-CLP-29 for any reason Subjects for whom the investigator considers study participation is no longer in the best interest of those subjects.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Atamestane|nan|
|Drug: toremifene|nan|
|Drug: letrozole|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In conjunction with the data from Biomed 777-CLP-29, compare the time to progression (TTP) in the atamestane plus toremifene arm to the TTP in the letrozole plus placebo arm |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In conjunction with the data from Biomed 777-CLP-29, obtain safety, survival and time to treatment failure (TTF) data for both arms in this continuation study. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atamestane, Breast neoplasms, Combined hormonal therapy, Complete estrogen blockade, Ductal breast carcinoma, Estrogen blocker, Fareston®, Femara®, First line therapy, Letrozole, Lobular breast carcinoma, Locally advanced breast cancer, Locally recurrent breast cancer, Maximal estrogen inhibition, Metastatic breast cancer, Neoplasms, Hormone-dependent, Receptor-positive, Stage IIIA breast cancer, Stage IIIB breast cancer, Stage IV breast cancer, Toremifene