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Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30

Phase 1
Completed
Conditions
Breast Cancer
Interventions
Other: biomarker analysis
Other: immunohistochemistry staining method
Other: liquid chromatography
Other: mass spectrometry
Registration Number
NCT00753207
Lead Sponsor
Cancer Trials Ireland
Brief Summary

RATIONALE: Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as epirubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lapatinib together with epirubicin may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of epirubicin when given together with lapatinib in treating patients with metastatic breast cancer.

Detailed Description

OBJECTIVES:

Primary

* To assess the safety and tolerability of fixed-dose lapatinib ditosylate in combination with epirubicin hydrochloride in patients with metastatic breast cancer.

* To determine the optimally-tolerated regimen in these patients.

Secondary

* To determine the clinical efficacy of this regimen in these patients.

* To analyze pharmacokinetic data of this regimen.

* To determine biomarkers that correlate with clinical benefit or response to lapatinib ditosylate in these patients.

Tertiary

* To identify tumor-derived or blood-derived biomarkers that correlate with or are predictive of clinical response or benefit to lapatinib ditosylate in these patients.

* To determine the levels of IGF-IR and phosphorylated IGF-IR in tumor tissue.

* To determine the expression pattern of the proteins associated with drug resistance that may be clinically active in these patients.

OUTLINE: This is a multicenter, dose-escalation study of epirubicin hydrochloride.

Patients receive oral lapatinib ditosylate followed by epirubicin hydrochloride IV over 15-30 minutes on day 1. Treatment repeats every 3 weeks for up to 7 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic analysis via liquid chromatography-mass spectometry (LC-MS).

After completion of study therapy, patients are followed at 28 days and then every 3 months thereafter.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
10
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Lapatinib and Epirubicinepirubicin hydrochlorideFixed dose of lapatinib in combination with escalating dose of epirubicin.
Lapatinib and Epirubicinlapatinib ditosylateFixed dose of lapatinib in combination with escalating dose of epirubicin.
Lapatinib and Epirubicinbiomarker analysisFixed dose of lapatinib in combination with escalating dose of epirubicin.
Lapatinib and Epirubicinimmunohistochemistry staining methodFixed dose of lapatinib in combination with escalating dose of epirubicin.
Lapatinib and Epirubicinliquid chromatographyFixed dose of lapatinib in combination with escalating dose of epirubicin.
Lapatinib and Epirubicinmass spectrometryFixed dose of lapatinib in combination with escalating dose of epirubicin.
Primary Outcome Measures
NameTimeMethod
Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride2012
Secondary Outcome Measures
NameTimeMethod
Pharmacokinetics2012
Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria2012
Correlation between baseline expression of intra-tumoral biomarkers (e.g., ErbB1, ErbB2, insulin-like growth factor-1 receptor, p-AKT, and ERK) and clinical response or benefit to lapatinib ditosylate by IHC2012
Correlation between expression pattern of drug resistance proteins (e.g., p-glycoprotein, MRP1, BCRP, and MDR-3) and clinical response or benefit to lapatinib ditosylate by IHC2012

Trial Locations

Locations (3)

St Vincent's University Hospital

🇮🇪

Dublin, Ireland

The Adelaide and Meath Hospital, Dublin Incorporating the National Childresn's Hospital

🇮🇪

Dublin, Ireland

St James's Hospital

🇮🇪

Dublin, Ireland

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