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RATIONALE: Aurora B/C kinase inhibitor GSK1070916A (GSK1070916A) 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 GSK1070916A in treating patients with advanced solid tumors.
- To determine and establish the safety profile of Aurora B/C kinase inhibitor GSK1070916A and define the dose-limiting toxicity in patients with advanced solid tumors.
- To determine the maximum-tolerated dose of Aurora B/C kinase inhibitor GSK1070916A in these patients.
- To determine plasma pharmacokinetic (PK) parameters following administration of Aurora B/C kinase inhibitor GSK1070916A in these patients.
- To evaluate tumor response after at least 1 cycle of treatment with Aurora B/C kinase inhibitor GSK1070916A in these patients.
- To propose a safe dose for Phase II evaluation.
- To investigate the effects of Aurora B/C kinase inhibitor GSK1070916A on markers of mitosis/cell proliferation and apoptosis in humans.
- To investigate the metabolism of Aurora B/C kinase inhibitor GSK1070916A in humans.
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive Aurora B/C kinase inhibitor GSK1070916A IV over 1 hour once daily on days 1-5. Courses repeat every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of Aurora B/C kinase inhibitor GSK1070916A until the maximum-tolerated dose (MTD) is determined. Once the MTD has been defined, 15-18 additional patients are recruited for an expanded MTD cohort in which patients receive Aurora B/C kinase inhibitor GSK1070916A at the MTD. Patients at the expanded MTD cohort must consent to have either tumor biopsies taken or FDG-PET/CT and DW-MRI scans performed.
Patients may undergo tissue, blood, and urine sample collection periodically for pharmacokinetic, pharmacodynamic, and other correlative laboratory studies.
After completion of study therapy, patients are followed up for 28 days.
Peer Reviewed and Funded or Endorsed by Cancer Research UK
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
Aurora B/C kinase inhibitor GSK1070916A, laboratory biomarker analysis, pharmacological study, diffusion-weighted magnetic resonance imaging, fludeoxyglucose F 18
Leeds Cancer Centre at St. James's University Hospital
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:13:53-0400
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