Metastatic HER2-negative breast cancer MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Xeloda
Pharmaceutical Form: Tablet
Sponsors
Centre Antoine-LACASSAGNE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age over 18, PS 0 to 2, Patients with metastatic HER2 negative breast cancer, Patient eligible to a treatment with capecitabine in monotherapy at 2000 mg/m2/D, 14 days every 21 days, Patient with a Uracilemia dosage performed following the French health recommendation Patients with at least one assessable lesion according to the RECIST criteria 1.1. Patients who have been informed and signed the informed consents (including the specific consent for DPYD genotyping), Patients with social coverage. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: PS> 2, Contraindication to Capecitabine treatment in monotherapy at 2000 mg/m2/D, 14 days every 21 days, Presence of known symptomatic cerebral or leptomeningeal metastases treated or uncontrolled (unstable corticosteroid requirements) and / or not clinically stable within 3 months before inclusion, History of cancer, with the exception of cancers in complete remission for more than 5 years, completely resected cutaneous basal cell carcinomas, in situ carcinomas or In situ cervical epithelioma treated, Vulnerable people as defined in Article L1121-5 to -8
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To analyze the influence of the DPD phenotype (DPD enzymatic activity in lymphoctye), on the objective response after 6 months of capecitabine given in monotherapy in patients with metastatic breast cancer.;Secondary Objective: - To analyze the influence of the DPD phenotype (uracilemia) on the objective response to treatment, - To compare DPD enzymatic activity in lymphocyte and uracilemia. - To define the threshold of DPD with risk of loss of therapeutic efficacy - To analyze the influence of DPD phenotype on overall survival - To analyze the influence of DPD phenotype on progression free survival - To analyze the influence of DPD phenotype on toxicities occurrences;Primary end point(s): The primary endpoint is the objective response to 6 months of measured treatment according to the RECIST 1.1 scale. The objective answer is defined as complete + partial response against stabilization + progression. This analysis will compare the objective response rate between patients with proficient DPD phenotype, measured by lymphocyte DPD activity (>3rd quartile, 25% of patients) and non-deficient DPD patients (phenotype between 13th and 75th percentiles).;Timepoint(s) of evaluation of this end point: 42 months (inclusion periode of 36 months + 6 months of treatment) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare the objective response rate (measured using the RECIST 1.1 scale) between patients with DPD proficient phenotype measured by the Uracilemia (at the 1st quartile ) The thresholds for high lymphocyte DPD activity associated with loss of therapeutic efficacy will be define by maximizing the sensibility of a predictive model for lack of response to treatment by capecitabine The correlation between the lymphocyte DPD activity and uracilemia will be assess with the Pearson correlation coefficient The overall survival will be define as the time between the date of inclusion and the date of death or the date of last news for those still alive at the end of the follow-up. The progression free survival will be define as the time between the date of inclusion and the date of death or progression or the date of last news for those still alive and progression free at the end of the follow-up. Toxicity will be evaluate using the CTCAE v5.0 - The overall survival at 5 years after the beginning of the treatment calculated between the date of inclusion and the date of breaking news at age 5 or death, - The 2-year progression-free survival calculated between the date of inclusion and the date of progression (defined according to RECIST v 1.1 criteria) or death or the date of the latest news for patients who have not progressed after 2 years, - The toxicity assessed using the Common Terminology Criteria for Adverse Events v4.03. - The concordance and correlation between these 4 markers will be compared in terms of sensitivity and specificity using ROC curves, correlation coefficient of Spearman and the Kappa concordance coefficient.;Timepoint(s) of evaluation of this end point: At the end of the study | — |
Countries
France
Contacts
Public ContactMaeva MAURIN-GODEMERT
Cantre Antoine-LACASSAGNE
Outcome results
None listed