Overview

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

Status:
Completed
Trial end date:
2009-03-01
Target enrollment:
0
Participant gender:
Female
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Hospices Civils de Lyon
Treatments:
Docetaxel
Epirubicin
Criteria
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