Lapatinib and Ixabepilone in Treating Patients With Advanced Solid Tumors (UCDCC#207)
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 ixabepilone, 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 ixabepilone may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of lapatinib given together with ixabepilone in treating patients with advanced solid tumors.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: lapatinib ditosylate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of Lapatinib (GW572016) in Combination With Weekly Ixabepilone (BMS 247550) in Advanced Solid Tumors|
- Safety and Toxicity [ Time Frame: Toxicity will be assessed at the beginning of every cycle and on day 8 and 15 of every cycle for at least eight weeks (2 cycles). Maximum of 6 cycles. ] [ Designated as safety issue: Yes ]Assessed by NCI CTCAE v 3.0
- Maximum tolerated dose (MTD) [ Time Frame: One cycle (4 weeks) ] [ Designated as safety issue: Yes ]
- Preliminary efficacy [ Time Frame: One year ] [ Designated as safety issue: No ]
|Study Start Date:||August 2009|
|Study Completion Date:||September 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
|Experimental: Lapatinib and Ixabepilone||
This intravenous treatment will be performed on an outpatient basis. Ixabepilone (15 - 20mg/m2) will be given weekly for 3 weeks, then one week off, every 28 days (4 weeks). The study doctor will decide how long to keep the participant on this treatment based on how the participant is tolerating the drug and how it is affecting the tumor.
Other Name: IxempraDrug: lapatinib ditosylate
Lapatinib (1000-1500 mg) will be administered orally on a daily basis. The study doctor will decide how long to keep the participant on this treatment based on how the participant is tolerating the drug and how it is affecting the tumor.
Other Name: Tykerb/Tyverb
- To evaluate the safety and feasibility of lapatinib ditosylate in combination with ixabepilone in patients with advanced solid tumors.
- To determine the maximum-tolerated dose of this regimen in these patients.
- To assess, preliminarily, the efficacy of this regimen in these patients.
- To perform laboratory correlative studies on tissue and blood specimens from these patients to investigate potential predictors of response.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive oral lapatinib ditosylate once daily on days 1-28 and ixabepilone IV on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Archival tumor tissue samples are collected for EGFR/HER2 pathway analyses via immunohistochemistry, mRNA analysis via RT-PCR, EGFR mutation analyses, Kras and braf mutation analysis via sequencing, and RAS mutations via PCR and sequencing. Blood samples are also collected periodically for tumor DNA and proteomics, acetylated alpha-tubulin analysis, EGFR-HER2 pathway genotypes, and pharmacogenomics.
After completion of study therapy, patients are followed for 30 days.
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010-3000|
|USC/Norris Comprehensive Cancer Center and Hospital|
|Los Angeles, California, United States, 90089-9181|
|University of California Davis Cancer Center|
|Sacramento, California, United States, 95817|
|United States, Louisiana|
|Feist-Weiller Cancer Center at Louisiana State University Health Sciences|
|Shreveport, Louisiana, United States, 71130-3932|
|Principal Investigator:||Helen K. Chew, MD||University of California, Davis|