NCT00483366

Imatinib Mesylate, Gemcitabine, and Capecitabine in Treating Patients With Advanced Solid Tumors

Phase I Study of Imatinib, Gemcitabine and Capecitabine in Patients With Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 13 (actual)
• Sponsor: University of Nebraska · Academic / Other
• Sex: All
• Age: 19 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as gemcitabine and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving imatinib mesylate together with gemcitabine and capecitabine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of gemcitabine and capecitabine when given together with imatinib mesylate in treating patients with advanced solid tumors.

Detailed description

OBJECTIVES: Primary * Determine the maximum tolerated dose of gemcitabine hydrochloride and capecitabine when combined with imatinib mesylate in patients with advanced solid tumors. * Determine the toxicity of this regimen in these patients. Secondary * Explore the antitumor activity of this regimen in these patients. OUTLINE: This is a dose-escalation study of gemcitabine and capecitabine. Patients receive oral imatinib mesylate once daily on days 1-5 and 8-12, gemcitabine hydrochloride IV on days 3 and 10, and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for at least 2 courses in the absence of progressive disease or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of gemcitabine hydrochloride and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Existing paraffin-embedded tissue blocks from patients diagnosed with melanoma or renal cell carcinoma will be assessed for c-kit mutations by polymerase chain reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and tyrosine kinase domain (exon 13 and 17). (Begins 12-11-2008) PROJECTED ACCRUAL: Closed to patient accrual 12/11/2008.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	capecitabine	Dose level Capecitabine -1 400 mg/m2 bid 0 500 mg/m2 bid 1. 500 mg/m2 bid 2. 600 mg/m2 bid 3. 600 mg/m2 bid 4. 725 mg/m2 bid 5. 725 mg/m2 bid 6. 850 mg/m2 bid 7. 850 mg/m2 bid
DRUG	gemcitabine hydrochloride	Dose level Gemcitabine -1 400 mg/m2 0 450 mg/m2 1. 550 mg/m2 2. 550 mg/m2 3. 675 mg/m2 4. 675 mg/m2 5. 825 mg/m2 6. 825 mg/m2 7. 1000 mg/m2
DRUG	imatinib mesylate	Dose level Imatinib -1 400 mg/d 0 400 mg/d 1. 400 mg/d 2. 400 mg/d 3. 400 mg/d 4. 400 mg/d 5. 400 mg/d 6. 400 mg/d 7. 400 mg/d
GENETIC	mutation analysis	C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.
GENETIC	nucleic acid sequencing	C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.
GENETIC	polymerase chain reaction	C-kit mutations will be assessed on existing paraffin-embedded blocks by Polymerase Chain Reaction and direct sequencing of both juxtamembrane domains (exons 9 and 11) and the tyrosine kinase domain (exons 13 and 17). Every ABI sequence will be compared to a NCBI Human KIT gene nucleotide sequence and will be blast using a NCBI Standard Nucleotide Blast Search to determine the presence of mutation within a particular exon.

Timeline

• Start date: 2006-08-15
• Primary completion: 2009-01-30
• Completion: 2011-03-29
• First posted: 2007-06-07
• Last updated: 2024-09-23

Locations

1 site across 1 country: United States