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

NCT ID: NCT02392845

Last Updated: 2015-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2009-03-31

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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination of Docetaxel (DTX) and Epirubicin (EPI)

Group Type: EXPERIMENTAL

Combination of Docetaxel (DTX) and Epirubicin (EPI)

Intervention Type: DRUG

Six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient

Interventions

Combination of Docetaxel (DTX) and Epirubicin (EPI)

Six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilles FREYER, Professor

Role: PRINCIPAL_INVESTIGATOR

Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud - Service d'oncologie médicale

Other Identifiers

2004.356

Identifier Type: -

Identifier Source: org_study_id