Clinical trial NCT02392845: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Keywords: Drug combination
Accelerated chemotherapy
Mathematical model
Hematotoxicity
Individualized dosage
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2015-03-19
Enrollment: 17
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Assessment of the risk of Dose-limiting Toxicities
timeFrame: 84 days (6 treatment cycles x 14 days)
Secondary outcomes:
measure: Plasma concentration of Docetaxel and Epirubicin after administration
timeFrame: 84 days (6 treatment cycles x 14 days)
measure: Tumor response for each patient with one or more measurable lesions
timeFrame: after 28 days (2 treatment cycles x 14 days) and 84 days (6 treatment cycles x 14 days)
measure: Progression-free survival
timeFrame: 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)
measure: Overall survival
timeFrame: 115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)
Other outcomes:
Locations:
Study officials:
affiliation: Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud - Service d'oncologie médicale
name: Gilles FREYER, Professor
role: PRINCIPAL_INVESTIGATOR
References: