A Pilot Dose Escalation Trial of a Densified Chemotherapy Association of Docetaxel and Epirubicin Driven by Mathematical Modeling in Metastatic Breast Cancer Patients: The MODEL1 Study
- Conditions
- Metastatic Breast Cancer
- Interventions
- Drug: Combination of Docetaxel (DTX) and Epirubicin (EPI)
- Registration Number
- NCT02392845
- Lead Sponsor
- Hospices Civils de Lyon
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 17
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination of Docetaxel (DTX) and Epirubicin (EPI) Combination of Docetaxel (DTX) and Epirubicin (EPI) -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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)