Phase II Pilot Study Assessing Efficacy of a Cisplatin - Métronomic Cyclophosphamide Treatment in Patients With Stade IV Triple Negative Breast Cancer Secondary Resistant to Anthracyclines and Taxanes

Study Overview
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Brief Summary
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Study assessing efficacy of a Cisplatine- Métronomic cyclophosphamide treatment in Patients with Metastatic Triple Negative breast Cancer Secondary Resistant to Anthracyclines and Taxanes.

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Performance status < 2, Patient with metastatic breast cancer stade IV triple negative histologically confirmed Measurable or not disease but radiologically evaluable (RECIST 1.1), Negative Hormonal Receptors (Estrogens and/or Progesterone), HER-2 negative (Score 0 or 1 by Immunochemistry (IHC), negative FISH if score IHC 2), Patient exposed to anthracyclines and/or taxanes in neo-adjuvant or adjuvant setting, Patient with a progression and for whom anthracyclines and/or taxanes treatment cannot be delivered and according to a resistance defined as : In the last 12 months after the last dose of taxanes or anthracyclines in adjuvant or neoadjuvant setting or, During or after a first metastatic chemtotherapy line and where taxanes and anthracyclines cannot be delivered according to : either a secondary resistance after an initial response to chemotherapy but a relapse observed either during the treatment or in the 4 months after the end of chemotherapy. either a sensitivity to treatment defined by a relapse after more than 4 months after the first chemotherapy metastatic line, either intolerance to anthracyclines (doxorubicin 240-400 mg/m² ou equivalent to doxorubicin (epirubicin) 300-550mg/m²) Patient non previously treated by platinum salts, Hematological Functions: Neutrophiles ≥ 1,5.109/L, Platelets ≥ 100.109/L, Leucocytes > 3 000/mm3, Hb > 9g/dL, Hepatic Functions : total Bilirubin ≤ 1,5 time upper normal value (UNV), ASAT ≤ 2 ,5 time UNV, ALAT ≤ 2,5 time UNV, Alkaline Phosphatase ≤ 2,5 time UNV (< 5 time UNV if case of hepatic metastasis), Renal Functions: Serum Creatinine ≤ 1,5 time UNV (and if value > 1,5 time UNV, so Clearance ≥ 60 mL/min) or Clearance ≥ 40 mL/min in case of RMI, Patient signed the consent study form, Patient affiliated to a social security regimen (law of 9 August 2004). Exclusion Criteria: Male Patients, Unknown hormonal Receptors Positive HER-2 (Score 3 in IHC or positive FISH) Pregnant or breastfeeding patient, or in age of pregnancy or predicting to be pregnant in the 6 months after the end of treatment, Patient not using contraceptive treatment during the treatment or after the 6 months after the end of treatment, Patient is a ward, Patient suffering from a non compatible disease with the enrollment in the study, Cardiac, renal, medullar, respiratory or hepatic insufficiency, clinically significant cardiovascular disease (including myocardiac infarct, unstable angina, symptomatic congestive heart failure, uncontrolled cardiac arrhythmia) < 1 year before the study enrollment or randomisation, Patient with pulmonary lymphangitis or symptomatic pleural effusion (grade≥2), meningeal known carcinoma or symptoms of cerebromeningeal invasion, brain metastases unless treatment and stability for at least 4 weeks (no steroids or anti-convulsive). Uncontrolled diabetes, Psychiatric or neurological significant abnormality, Peripheric Neuropathy > grade 2, Antecedent of hypersensibility to one of study treatment or one of used excipients, Urinary tract infection or acute hemorrhagic cystitis in progress Concomitant treatment with a medicine containing phenytoin or medication received in the context of a trial, or participation in another therapeutic clinical trial within <30 days prior treatment with chemotherapy. Geographically unstable patient in the next 6 months or remaining distance to the treatment center making it difficult to follow in the study, Known history of abuse of narcotic or other drug or alcohol History of surgery within 28 days before the start of treatment, Patient unwilling or unable to comply with the requirements 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin - Metronomic Cyclophosphamide<br>Cisplatin 25 mg/m² from day 1 to day 3 every 3 weeks Metronomic Cyclophosphamide 150 mg from day 1 to day 14 every 3 weeks | Drug: Cisplatin<br>* 25 mg/m² I.V. from day 1 to day 3 - total dose = 75 mg/m² every 3 weeks<br>Drug: Cyclophosphamide<br>* Metronomic cyclophosphamide per os 150 mg from day 1 to day 14 - total dose 2100 mg every 3 weeks<br>* Other names: Endoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate of cisplatine - metronomic cyclophosphamide treatment |  | 12 months and 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free progression |  | 3 years | 
| Safety profile of cisplatin - metronomic cyclophosphamide association | Number of Participants with Adverse Events | 12 months and 6 weeks | 
| Overall survival |  | 5 years | 
| Predictive factors to response and/or resistance treatment |  | 12 months and 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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triple negative breast cancer, late-relapse