Metastatic Breast Cancer
Conditions
Keywords
Drug combination, Accelerated chemotherapy, Mathematical model, Hematotoxicity, Individualized dosage
Brief summary
To determine the maximum tolerated dose of a densified regimen of the association of docetaxel (DTX) and epirubicin (EPI), supported by the concomitant administration of hematopoietic growth factors in patients with metastatic breast cancer in first-line, optimizing in each patient the administration schedule using a formal procedure based on mathematical models in order to manage the severity of induced neutropenia. The models used in this project allow: * an optimal administration schedule of the planned total dose per cycle (number of infusions and calculating their rates and durations) * an individualization of the administration schedule from the second cycle (based on observations from the first cycle), and * an assessment of the risk of a dose-limiting toxicity event combining several severe non-hematological toxicities (conditioning the decision for dose escalation). Using formal mathematical models the investigators expect controlling the hematological and non-hematological toxicities in order to realize the full series of six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient. For each patient, chemotherapy is considered feasible if it is possible, in the absence of tumor progression, to consider 6 cycles of treatment without observing any serious adverse events and without: * patient death that may be related to the treatments; * decision of the patient to interrupt treatment for physical or psychological tolerance reasons; * decision of the investigator to discontinue treatment, in the absence of disease progression.
Interventions
DRUGCombination of Docetaxel (DTX) and Epirubicin (EPI)
Six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, * ECOG performance status ≤ 2 * Diagnosed with metastatic HER2-negative hormone-resistant chemotherapy-naive breast cancers, previous adjuvant chemotherapy treatment are allowed. * Histologically or cytologically proven breast cancer metastases or associated with CA 15-3 levels 50% above the normal value * Hormone resistance defined by the presence of negative hormone receptors or disease progression within 6 months of the initiation of hormone therapy. * Adequate renal and liver function (ASAT and ALAT \< twice the upper limit normal value (ULN) if no liver metastases, or \< 4×ULN if liver metastases; total bilirubin \< 2×ULN), * Adequate cardiac function (left ventricular ejection fraction (LVEF) \> 50%), * Neutrophils ≥ 1200/mm3 * Platelets ≥ 105/mm3
Exclusion criteria
* Cerebral metastases and meningeal involvement, * Other malignant diseases, * Significant comorbidities, * Previous chemotherapy for metastatic disease, or previous chemotherapy with a total cumulative dose greater than 600 mg/m² for EPI or greater than 450 mg/m² for DTX
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of the risk of Dose-limiting Toxicities | 84 days (6 treatment cycles x 14 days) | DLTs were defined as ≥ grade 3 vomiting, ≥ grade 3 mucositis,≥ grade 3 hand-foot syndrome (HFS), grade 2 vomiting plus grade 2 mucositis, or grade 2 vomiting plus grade 2 HFS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration of Docetaxel and Epirubicin after administration | 84 days (6 treatment cycles x 14 days) | Assessment of the pharmacokinetics of Docetaxel and Epirubicin |
| Tumor response for each patient with one or more measurable lesions | after 28 days (2 treatment cycles x 14 days) and 84 days (6 treatment cycles x 14 days) | Measurement of tumor response by MRI for each patient with one or more measurable lesions, classified according to RECIST criteria |
| Progression-free survival | 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available) | — |
| Overall survival | 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available) | — |
Countries
France
Contacts
PRINCIPAL_INVESTIGATORGilles FREYER, Professor
Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud - Service d'oncologie médicale
Outcome results
None listed