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 (MODEL1)

June 9, 2026 updated by: Hospices Civils de Lyon

A Pilot Dose Escalation Phase I Trial of a Densified Chemotherapy Association of Docetaxel and Epirubicin Driven by Mathematical Modeling in Metastatic Breast Cancer Patients: The MODEL1 Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

17

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69002
        • Gilles FREYER , Professor 04 78 86 43 18 Ext. +33 gilles.freyer@chu-lyon.fr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination of Docetaxel (DTX) and Epirubicin (EPI)
Drug: Combination of Docetaxel (DTX) and Epirubicin (EPI)
Six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assessment of the risk of Dose-limiting Toxicities
Time Frame: 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
84 days (6 treatment cycles x 14 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma concentration of Docetaxel and Epirubicin after administration
Time Frame: 84 days (6 treatment cycles x 14 days)
Assessment of the pharmacokinetics of Docetaxel and Epirubicin
84 days (6 treatment cycles x 14 days)
Tumor response for each patient with one or more measurable lesions
Time Frame: 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
after 28 days (2 treatment cycles x 14 days) and 84 days (6 treatment cycles x 14 days)
Progression-free survival
Time Frame: 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)
115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)
Overall survival
Time Frame: 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)
115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Gilles FREYER, Professor, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud - Service d'oncologie médicale

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

March 3, 2015

First Submitted That Met QC Criteria

March 13, 2015

First Posted (Estimated)

March 19, 2015

Study Record Updates

Last Update Posted (Actual)

June 10, 2026

Last Update Submitted That Met QC Criteria

June 9, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2004.356

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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