Lapatinib and Epirubicin in Treating Patients With Metastatic Breast Cancer. ICORG 06-30
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.
Drug: epirubicin hydrochloride
Drug: lapatinib ditosylate
Other: biomarker analysis
Other: immunohistochemistry staining method
Other: liquid chromatography
Other: mass spectrometry
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Phase I Study of Fixed Dose Lapatinib in Combination With an Escalating Dose of Epirubicin in Metastatic Breast Cancer|
- Optimally-tolerated regimen of lapatinib ditosylate in combination with epirubicin hydrochloride [ Time Frame: 2012 ] [ Designated as safety issue: Yes ]
- Efficacy of this regimen in terms of objective tumor response rate and disease progression as assessed by standard RECIST criteria [ Time Frame: 2012 ] [ Designated as safety issue: No ]
- Pharmacokinetics [ Time Frame: 2012 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: 2012 ] [ Designated as safety issue: No ]
- 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 [ Time Frame: 2012 ] [ Designated as safety issue: No ]
|Study Start Date:||October 2007|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
Experimental: Lapatinib and Epirubicin
Fixed dose of lapatinib in combination with escalating dose of epirubicin.
|Drug: epirubicin hydrochloride Drug: lapatinib ditosylate Other: biomarker analysis Other: immunohistochemistry staining method Other: liquid chromatography Other: mass spectrometry|
- 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.
- 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.
- 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.
|St Vincent's University Hospital|
|Dublin, Ireland, 4|
|St James's Hospital|
|Dublin, Ireland, 8|
|The Adelaide and Meath Hospital, Dublin Incorporating the National Childresn's Hospital|
|Dublin, Ireland, 24|
|Principal Investigator:||John Crown, MD||St. Vincent's University Hospital|