Evaluation of the Efficacy of Estramustine in Patient With Breast Cancer Progression After Treatment With Aromatase Inhibitor.

Study Overview
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Brief Summary
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Despite advances in early detection and treatment strategy, about 25 to 40% of patients treated for breast cancer develop metastasis. Some patients are in a therapeutic impasse situation. It is therefore necessary to consider all possible options. The Estramustine showed encouraging results in the treatment of metastatic breast cancer. Given the clinical data, the answer rate of Estramustine and its impact on progression free survival deserve to be studied in earlier clinical situation. This Phase II study evaluated the efficacy of Estramustine in women with breast cancer and metastates, already treated with aromatase inhibitors and for whom this treatment has failed.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Estramustine
* Drug: Tamoxifen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-menopausal women or women receiving Luteinizing hormone-releasing hormone (LHRH) analogs Histologically confirmed metastatic breast cancer RH+ Measurable metastatic breast cancer (modified RECIST criteria) or not measurable but evaluable Recurrence: being treated with aromatase inhibitors (AIs) after adjuvant treatment by AIs after progression of the metastatic cancer in patients receiving AIs following positive response during at least 6 months Performance status ≤ 2 Haematological test: polynuclear neutrophiles ≥ 1.5 × 109 /L, haemoglobin ≥ 9 g/dL, blood platelet ≥ 100 × 109 /L Hepatic function: albumin ≥ 2.5 g/dL, serum bilirubin ≤ 1.5 × N (except if Gilbert's Syndrome) , aminotransferases ≤ 3 × N (≤ 5 × N if hepatic metastases) Renal function: serum creatinine ≤ 1.5 mg/dL or clearance of creatinine ≥ 40 ml/min Women without endometrial pathology Ability to provide written informed consent before the start of any study specific procedures Exclusion Criteria: Age < 18 years old Pre-menopausal, pregnant or pregnant or breast feeding females Patient who should exclusively be treated by chemotherapy Women previously treated with chemotherapy but not by AIs Women previously treated by tamoxifen for their metastatic breast cancer HER2+ Concurrent anti-cancer treatment (chemotherapy, surgery, immunotherapy, biological therapy and tumour embolism) Concurrent treatment with protocol-defined prohibited medications Malabsorption syndrome , significant digestive dysfunction, gastrectomy, jejunectomy, hemorrhagic recto colon Concurrent disease or condition that may interfere with study participation, or any serious medical disorder that would interfere with the subject's safety (for example, active or uncontrolled infection or any psychiatric condition prohibiting understanding or rendering of informed consent) Any pathology, including severe psychiatric or psychologic disease that may harm patient's safety or participation in the study Serious or not cured or unstable toxicity due to the administration of another drug being involved in clinical trials Uncontrolled cardiovascular pathologies Previous history of thromboembolic event like deep vein thrombosis or pulmonary embolism recorded within one year before the inclusion date Active uncontrolled infection Existence of an increased risk of thromboembolic event, apart from the metastatic cancer condition, such as: known presence of antiphospholipid antibody family history of thrombophilia existence of any clinical, genetic, or biological abnormality which can increase the risk of thromboembolic event according to the Participation to a clinical trial at least 4 weeks prior the start of the study

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: GROUP E (Estramustine)<br>Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by estramustine | Drug: Estramustine<br>* 140mg/4 caps/day<br>* Other names: estramustine phosphate;|
| Other: GROUP T (Tamoxifen)<br>Patients with HER2-/RH+ breast cancer progressing after having already undergone a first line adjuvant treatment by tamoxifen | Drug: Tamoxifen<br>* 20mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival after a 6- month monotherapy with Estramustine in patients with HER2-/RH+ breast cancer progressing | proportion of patients in progression-free survival (PFS) after a 6-month treatment is defined as the duration of objective response or stabilisation of the disease according to the Recist criteria. The following events shall be considered as progressive : Relapse Treatment intolerance leading to stop the treatment Death | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risks of thrombosis | risks of thrombosis assessed by the analysis of biomarkers (D-Dimer, prothrombin fragment 1+2, von Willebrand factor, fibrinogen, Chain Reaction Protein) | up to 6 months | 
| Clinical benefit of estramustine | clinical benefit of estramustine assessed by RECIST criteria | 1 year | 
| Correlation between the answer rate and biomarkers | answer rate (RECIST criteria) and level of biomarkers (Lactate déshydrogénase, Antigène carcino-embryonnaire and Cancer antigène 15-3) | 1 year | 
| Tolerance of estramustine treatment | Toxicity (Common Terminology Criteria for Adverse Events) | 1 year | 
| Tolerance of tamoxifen treatments | Toxicity (Common Terminology Criteria for Adverse Events) | 1 year | 
| Proportion of patients developing thromboembolic events | proportion of patients developing thromboembolic events assessed in the 2 groups every month during the one-year patient follow-up | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aromatase inhibitors, Metastases