Breast Cancer
Conditions
Keywords
aromatase inhibitors, Metastases
Brief summary
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.
Interventions
DRUGEstramustine
140mg/4 caps/day
DRUGTamoxifen
20mg/day
Sponsors
Institut de Cancérologie de Lorraine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival after a 6- month monotherapy with Estramustine in patients with HER2-/RH+ breast cancer progressing | up to 6 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical benefit of estramustine | 1 year | clinical benefit of estramustine assessed by RECIST criteria |
| Correlation between the answer rate and biomarkers | 1 year | answer rate (RECIST criteria) and level of biomarkers (Lactate déshydrogénase, Antigène carcino-embryonnaire and Cancer antigène 15-3) |
| Risks of thrombosis | up to 6 months | risks of thrombosis assessed by the analysis of biomarkers (D-Dimer, prothrombin fragment 1+2, von Willebrand factor, fibrinogen, Chain Reaction Protein) |
| Tolerance of tamoxifen treatments | 1 year | Toxicity (Common Terminology Criteria for Adverse Events) |
| Proportion of patients developing thromboembolic events | 1 year | proportion of patients developing thromboembolic events assessed in the 2 groups every month during the one-year patient follow-up |
| Tolerance of estramustine treatment | 1 year | Toxicity (Common Terminology Criteria for Adverse Events) |
Countries
France
Outcome results
None listed