Dasatinib and Lapatinib in Treating Patients With Advanced Solid Tumors That Cannot Be Removed By Surgery
RATIONALE: Dasatinib and lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of dasatinib and lapatinib when given together in treating patients with advanced solid tumors that cannot be removed by surgery.
Unspecified Adult Solid Tumor, Protocol Specific
Drug: lapatinib ditosylate
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I Trial of the Combination of Dasatinib and Lapatinib|
- Maximum tolerated dose [ Designated as safety issue: Yes ]
- Adverse events profile [ Designated as safety issue: Yes ]
- Toxicity profile [ Designated as safety issue: Yes ]
- Response profile [ Designated as safety issue: No ]
- Time to progression [ Designated as safety issue: No ]
- Time to treatment failure [ Designated as safety issue: No ]
|Study Start Date:||August 2008|
|Estimated Primary Completion Date:||September 2014 (Final data collection date for primary outcome measure)|
- Determine the maximum tolerated dose of dasatinib combined with lapatinib ditosylate.
- Describe the toxicities associated with this treatment combination.
- Assess the pharmacokinetic interaction of lapatinib ditosylate and dasatinib.
- Assess the effect of the lapatinib ditosylate and dasatinib combination on circulating tumor cells and on osteoclast precursor activation.
- Study the association of clinical (toxicity and/or tumor response or activity) with the pharmacokinetic parameters, and/or biologic (pharmacodynamic) results.
- Describe the responses of this treatment combination.
OUTLINE: This is a multicenter study.
- Cohort I (determination of maximum tolerated dose [MTD]): Patients receive oral dasatinib and oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Cohort II (treatment at the MTD): Patients receive oral dasatinib once daily on days 1 and 9-28, and oral lapatinib ditosylate once daily on days 2-28 of course 1. For all subsequent courses, patients receive oral dasatinib and oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Tissue and blood samples are collected periodically for pharmacokinetic and correlative studies. Samples are analyzed for biomarkers, circulating tumor cells, tyrosine phosphorylated or total MAP-K, EGFR, Her2, and FAK, among other potential markers of activity and/or response by immunofluorescence. Circulating osteoclasts are also assessed by flow cytometry.
After completion of treatment study, patients are followed for 3 months.
|United States, Arizona|
|Mayo Clinic in Arizona|
|Scottsdale, Arizona, United States, 85259-5499|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 32224|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Study Chair:||Charles Erlichman, MD||Mayo Clinic|
|Principal Investigator:||Donald Northfelt, M.D.||Mayo Clinic|
|Principal Investigator:||Michael Menefee, M.D.||Mayo Clinic|