Evaluation and Modeling of the Effect of G-CSF on the Evolution of Polynuclear Neutrophils During Dense Dose Epirubicin-Cyclophosphamide Regeneration

Study Overview
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Brief Summary
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Patients including of localized breast cancer will require chemotherapy treatment with epirubicin - cyclophosphamide (EC) followed by treatment with docetaxel or paclitaxel. In addition to this chemotherapy, the investigator will prescribe injections of granulocyte growth factors (G-CSF), to stimulate the growth of white blood cells. Patients will be randomized to either a peg-G-CSF arm or a G-CSF arm, prescribed at different times. The aim is to determine whether one of the two treatment regimens best limits the risk of a decrease in white blood cells

Detailed Description
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For this tudy : patients will be randomized to either : with administration of peg-G-CSF (administration on D2) with administration of G-CSF (administration on D4 to D7 or D8) This study aims to model the effect of exogenous G-CSF for the evolution of polymorphonuclear neutrophils as a function of time and to explain the pharmacodynamic variability during the administration of chemotherapy such as EC-dense dose administered as an adjuvant or neo-adjuvant in patients treated for localized breast cancer.

Official Title
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Evaluation and Modeling of the Effect of G-CSF on the Evolution of Polynuclear Neutrophils During Dense Dose Epirubicin-Cyclophosphamide Regeneration

Conditions
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Localized Breast Cancer

Intervention / Treatment
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* Drug: Dense dose epirubicin-cyclophosphamide chemotherapy and G-CSF (filgrastim, lenograstim)
* Drug: Dense dose epirubicin-cyclophosphamide chemotherapy with administration of peg-G-CSF (pegfilgrastim)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women Patient over 18 years old Patient with histologically documented, non-metastatic breast cancer who must receive dense dose Epirubicin-Cyclophosphamide (EC) type treatment as part of neoadjuvant or adjuvant treatment Patient to receive granulocyte growth factors (G-CSF or peg-G-CSF) as a preventive measure from the first cycle Neutrophils > 1,500 /mm3; platelets > 100,000 /mm3 Written informed consent, dated and signed For patients of childbearing age, effective means of contraception during treatment and up to 3 months after stopping treatment Exclusion Criteria: Patient with a contraindication to treatment with anthracyclines Patient already undergoing treatment with EC dense dose Patient with a contraindication to treatment with G-CSF such as hypersensitivity to the active ingredient or to one of the excipients Pregnant or breastfeeding women Patient under guardianship or curatorship or subject to a protection regime for adults Patient not affiliated to a social security scheme (beneficiary or beneficiary)

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized : Either to a peg-G-CSF arm (with administration of peg-G-CSF on D2) Either to a G-CSF arm (with administration from D4 to D7 or D8). Blood samplig will be taken at D1, D4, D8 and D14 for each arm.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 : Dense dose epirubicin-cyclophosphamide chemotherapy with administration of G-CSF<br>2 cycles of chemotherapy with administration of G-CSF (filgrastim or lenograstim) on D2, D4 to D7 or D8.. Realization of blood sampling at D1, D4, D8 and D14 | Drug: Dense dose epirubicin-cyclophosphamide chemotherapy and G-CSF (filgrastim, lenograstim)<br>* - Arm 1: 2 cycles of chemotherapy with administration of G-CSF (filgrastim or lenograstim) on D2, D4 to D7 or D8.. Realization of blood sampling at D1, D4, D8 and D14<br>|
| Experimental: Arm 2 : Dense dose epirubicin-cyclophosphamide chemotherapy with administration of peg-G-CSF<br>2 cycles of chemotherapy with administration of peg-G-CSF (pegfilgrastim) on D2. Realization of blood sampling at D1, D4, D8 and D14 | Drug: Dense dose epirubicin-cyclophosphamide chemotherapy with administration of peg-G-CSF (pegfilgrastim)<br>* - Arm 2: 2 cycles of chemotherapy with administration of peg-G-CSF (pegfilgrastim) on D2. Realization of blood sampling at D1, D4, D8 and D14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variation of Neutrophils concentration in patient treated with G-CSF or peg-G-CSF | Variation of Neutrophils concentration will be assess by blood count formula performed during the 2 first cycle of Epirubicin-cyclophosphamide treatment. | Day 4 | 
| Variation of Neutrophils concentration in patient treated with G-CSF or peg-G-CSF | Variation of Neutrophils concentration will be assess by blood count formula performed during the 2 first cycle of Epirubicin-cyclophosphamide treatment. | Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, G-CSF, Epirubicin-cyclophosphamide dose-dense