An Open-Label Phase I Study of Fixed Dose Lapatinib in Combination With an Escalating Dose of Epirubicin in Metastatic Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- epirubicin hydrochloride
- Conditions
- Breast Cancer
- Sponsor
- Cancer Trials Ireland
- Enrollment
- 10
- Locations
- 3
- Primary Endpoint
- Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: epirubicin hydrochloride
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: lapatinib ditosylate
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: biomarker analysis
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: immunohistochemistry staining method
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: liquid chromatography
Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
Intervention: mass spectrometry
Outcomes
Primary Outcomes
Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride
Time Frame: 2012
Secondary Outcomes
- Pharmacokinetics(2012)
- Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria(2012)
- 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 IHC(2012)
- 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 IHC(2012)