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

NCT02392845 | Completed Phase 1

• 1 other identifier: 2004.356
• Study Type: interventional
• Target: 17
• Locations: 0 countries
• Sites: N/A

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

Keywords

Drug combination; Accelerated chemotherapy; Mathematical model; Hematotoxicity; Individualized dosage

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (4)

• Plasma concentration of Docetaxel and Epirubicin after administration

  84 days (6 treatment cycles x 14 days)

• Tumor response for each patient with one or more measurable lesions

  after 28 days (2 treatment cycles x 14 days) and 84 days (6 treatment cycles x 14 days)

• Progression-free survival

  115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)

• Overall survival

  115 days (study duration (6 treatment cycles x 14 days) + follow-up (31 days) when available)

Study Arms (1)

Combination of Docetaxel (DTX) and Epirubicin (EPI)

EXPERIMENTAL

Drug: Combination of Docetaxel (DTX) and Epirubicin (EPI)

Interventions

Combination of Docetaxel (DTX) and Epirubicin (EPI) DRUG

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

Combination of Docetaxel (DTX) and Epirubicin (EPI)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Gilles FREYER, Professor

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2015
• First Posted: March 19, 2015
• Study Start: June 1, 2005
• Primary Completion: March 1, 2009
• Study Completion: March 1, 2009
• Last Updated: March 19, 2015

Record last verified: 2015-03