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
Information source: Hospices Civils de Lyon
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Breast Cancer
Intervention: Combination of Docetaxel (DTX) and Epirubicin (EPI) (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Hospices Civils de Lyon Official(s) and/or principal investigator(s): Gilles FREYER, Professor, Principal Investigator, Affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud - Service d'oncologie médicale
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.
Clinical Details
Official title: 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
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Assessment of the risk of Dose-limiting Toxicities
Secondary outcome: Plasma concentration of Docetaxel and Epirubicin after administrationTumor response for each patient with one or more measurable lesions Progression-free survival Overall survival
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
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
Locations and Contacts
Additional Information
Starting date: June 2005
Last updated: March 13, 2015
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