Study Assessing Efficacy of ZARNESTRA™ Combined With Tamoxifen in Patients With Advanced or Metastatic Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the objective response rate when ZARNESTRA is added to treatment with tamoxifen

Official Title
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Open, Single-Arm Phase II Study Assessing Efficacy of ZARNESTRA™ Combined With Tamoxifen in Patients With Advanced or Metastatic Breast Cancer Expressing the Estrogen and/or Progesterone Receptor

Conditions
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Breast Neoplasms

Intervention / Treatment
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* Drug: Tamoxifen
* Drug: Zarnestra


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven, metastatic or locally advanced inoperable breast cancer Tumor considered potentially hormone-sensitive, i.e. presence by IHC of hormone receptors for estrogens (ER+ for more than 10% of cells) and/or progesterone (Pg+ for more than 10% of cells) or both. This expression may have been detected on the primary tumor or at a metastatic site. The method used will be reassessed by IHC if it involves a radioligand technique whenever it is possible to obtain histological material. Progressing on treatment with tamoxifen, given either as adjuvant treatment or for advanced/metastatic breast cancer. Any previous treatment with a steroidal or nonsteroidal antiaromatase in a neo-adjuvant, adjuvant or metastatic situation is permitted. Likewise, any previous treatment with chemotherapy and/or herceptin in a nonmetastatic situation is permitted. Post-menopausal patients Age > 18 years At least one measurable lesion according to the Response Evaluation Criteria for Solid Tumors (RECIST) criteria; for patients who only have bone metastases, an evaluable non-irradiated lytic lesion is required Performance Status (WHO): PS ≤ 2 (Appendix 1). Laboratory tests in accordance with the following criteria: Neutrophils ≥ 2x109/l,Platelets ≥ 100x109/l,Hemoglobin ≥ 10 g/dl, ASAT, ALAT ≤ 2.5 N , or < 5 N when liver metastasis,bilirubin ≤ 1.5 N creatinin ≤ 1.5 N Signed, written consent before any study-related procedure Exclusion Criteria: Men Pre-menopausal patients who are not receiving concurrent LHRH agonist therapy ER- and PR-negative patients Contraindication to antiestrogens (thromboembolic risk) or ZARNESTRA Non metastatic tumor susceptible to management by radiotherapeutic and/or surgical means T4d inflammatory tumor (PEV 2 or 3). Short-term, life-threatening lesions: hepatic invasion > 1/3 of liver volume, pulmonary lymphangitis, uncontrolled cerebral metastases, carcinomatous meningitis Sensory neuropathy > or = grade 1 (WHO) Previous history of uncontrolled cancers or controlled for less than 5 years, except basal cell skin cancers and in situ cancers of the cervix. Chronic diseases (somatic or psychiatric) with a poor prognosis subjects with enzyme-inducing anti-convulsants (e.g., phenytoin, phenobarbital, carbamazepine) : this treatment is not permitted while taking ZARNESTRA Patients who, for family, social, geographic or psychological reasons, could not be followed up correctly.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tamoxifen|nan|
|Drug: Zarnestra|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the objective response rate when ZARNESTRA is added to administration of tamoxifen in patients suffering from metastatic or advanced inoperable breast cancer, who are progressing on tamoxifen treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the time to progression |  |  | 
| To evaluate the clinical benefit (response + stable disease at 6 months) |  |  | 
| To evaluate the safety of the combination ZARNESTRA and tamoxifen |  |  | 
| To evaluate a possible pharmacokinetic interaction between ZARNESTRA and tamoxifen |  |  | 
| To evaluate the biological predictive and prognostic factors of a response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Neoplasms, Zarnestra, Tamoxifen, estrogen receptor, progesterone receptor