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

Metastatic Breast Cancer Clinical Trial

— MODEL1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02392845
• Other study ID #: 2004.356
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2015
• Last updated: March 13, 2015
• Start date: June 2005
• Est. completion date: March 2009

Study information

• Verified date: March 2015
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Française de Sécurité Sanitaire des Produits de Santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Combination of Docetaxel (DTX) and Epirubicin (EPI)
Six cycles of densified DTX+EPI chemotherapy (2 weeks per cycle) for each patient

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of the risk of Dose-limiting Toxicities	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)	Yes
Secondary	Plasma concentration of Docetaxel and Epirubicin after administration	Assessment of the pharmacokinetics of Docetaxel and Epirubicin	84 days (6 treatment cycles x 14 days)	No
Secondary	Tumor response for each patient with one or more measurable lesions	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)	No
Secondary	Progression-free survival		115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)	No
Secondary	Overall survival		115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)	No