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

Civil Hospices of Lyon

Status and phase: Completed; Phase 1

Conditions: Metastatic Breast Cancer

Treatments: Drug: Combination of Docetaxel (DTX) and Epirubicin (EPI)

Study type: Interventional

Funder types: Other

Identifiers

NCT02392845

2004.356

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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17 participants in 1 patient group

Combination of Docetaxel (DTX) and Epirubicin (EPI)

Experimental group

Treatment:

Drug: Combination of Docetaxel (DTX) and Epirubicin (EPI)