Aurora B/C Kinase Inhibitor GSK1070916A in Treating Patients With Advanced Solid Tumors
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.
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: Aurora B/C kinase inhibitor GSK1070916A Other: laboratory biomarker analysis Other: pharmacological study Procedure: diffusion-weighted magnetic resonance imaging + PET CT Radiation: fludeoxyglucose F 18 dynomic contrast||Phase 1|
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Cancer Research UK Phase I Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Aurora B Inhibitor GSK1070916A in Patients With Advanced Solid Tumors|
- Causality of each adverse event to Aurora B/C kinase inhibitor GSK1070916A and grading severity according to NCI CTCAE Version 4.02
- Maximum-tolerated dose (MTD)
- Measurement of PK parameter values for Aurora B/C kinase inhibitor GSK1070916A including AUC, Cmax, Tmax, and half life (all cohorts)
- Response assessment (stable disease, partial response, or complete response)
- Analysis of phosphohistone H3, Ki67, and cleaved caspase 3 in skin-punch biopsies (all cohorts) and tumor biopsies (at the MTD only)
- Analysis of caspase-cleaved cytokeratin 18 in serum samples (all cohorts)
- Investigation of metabolite concentration in samples of blood (all cohorts) and urine (at the MTD only)
- Safe dose for phase II evaluation
|Study Start Date:||March 2010|
|Study Completion Date:||March 2013|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
- 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01118611
|Leeds Cancer Centre at St. James's University Hospital|
|Leeds, England, United Kingdom, LS9 7TF|
|Barts and the London School of Medicine|
|London, England, United Kingdom, EC1M 6BQ|
|Principal Investigator:||Chris Twelves, MD, BMedSci, FRCP||Leeds Cancer Centre at St. James's University Hospital|