Imatinib Mesylate, Gemcitabine, and Capecitabine in Treating Patients With Advanced Solid Tumors
Condition: Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Neoplasms
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): capecitabine; gemcitabine hydrochloride; imatinib mesylate; mutation analysis; nucleic acid sequencing; polymerase chain reaction
Intervention type(s): Drug; Drug; Drug; Genetic; Genetic; Genetic
Intervention description(s): Dose level Capecitabine
-1 400 mg/m2 bid
0 500 mg/m2 bid
500 mg/m2 bid
600 mg/m2 bid
600 mg/m2 bid
725 mg/m2 bid
725 mg/m2 bid
850 mg/m2 bid
850 mg/m2 bid; Dose level Gemcitabine
-1 400 mg/m2 0 450 mg/m2
550 mg/m2
550 mg/m2
675 mg/m2
675 mg/m2
825 mg/m2
825 mg/m2
1000 mg/m2; Dose level Imatinib
-1 400 mg/d 0 400 mg/d
400 mg/d
400 mg/d
400 mg/d
400 mg/d
400 mg/d
400 mg/d
400 mg/d; 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.; 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.; 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.
Other intervention name(s): Xeloda; Gemzar; Gleevec
Intervention MeSH terms: Gemcitabine; Capecitabine; Imatinib Mesylate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified adult solid tumor, protocol specific