Lapatinib and Doxorubicin Hydrochloride Liposome in Treating Patients With Metastatic Breast Cancer
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 doxorubicin hydrochloride liposome 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 doxorubicin hydrochloride liposome may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of doxorubicin hydrochloride liposome when given together with lapatinib in treating patients with metastatic breast cancer.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of Lapatinib in Combination With Liposomal Doxorubicin in Patients With Metastatic Breast Cancer|
- Cardiac safety [ Time Frame: Throughout treatment and up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Time Frame: After the first cycle of therapy ] [ Designated as safety issue: Yes ]
- Pharmacokinetic profiles [ Time Frame: After treatment completion for 12 patients treated at the maximum tolerated dose ] [ Designated as safety issue: No ]
- Efficacy [ Time Frame: At time of disease progression ] [ Designated as safety issue: No ]
|Study Start Date:||May 2006|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
|Experimental: Lapatinib Ditosylate and Doxil||
Drug: lapatinib ditosylate
1500 mg orally daily for as long as patients remain on trial (up to 8 cycles).Drug: Doxil
Administered intravenously (IV) every 4 weeks in a dose-escalating fashion according to a set schedule
- Evaluate the safety, tolerability, and feasibility of pegylated doxorubicin HCl liposome (PLD) when administered with lapatinib, particularly in terms of cardiac safety, in patients with metastatic breast cancer.
- Determine the optimally tolerated regimen (OTR) of PLD when administered with lapatinib in these patients.
- Determine the pharmacokinetic profiles of lapatinib and PLD when given in combination at the OTR.
- Describe any preliminary evidence of efficacy of lapatinib and PLD in these patients.
OUTLINE: This is an open-label, dose-escalation study of pegylated doxorubicin HCl liposome (PLD).
Patients receive oral lapatinib once daily on days 1-28 and PLD IV over at least 30 minutes on day 1. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Lapatinib may be continued alone in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of PLD until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose-limiting toxicity.
After completing study treatment, patients are followed for 30 days.
PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00316875
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University|
|Chicago, Illinois, United States, 60611-3013|
|Principal Investigator:||William J Gradishar, M.D.||Robert H. Lurie Cancer Center|