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 (META2)

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

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Cyclophosphamide

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63011
    • Centre Jean Perrin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Centre Jean Perrin

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (ACTUAL): September 1, 2016
• Study Completion (ACTUAL): September 1, 2016

Study Registration Dates

• First Submitted: May 28, 2013
• First Submitted That Met QC Criteria: July 29, 2013
• First Posted (ESTIMATE): July 30, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 11, 2016
• Last Update Submitted That Met QC Criteria: October 10, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: triple negative breast cancer; late-relapse
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Cisplatin
• Other Study ID Numbers: CJP 4.2 - META2