AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors
RATIONALE: AT9283 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 AT9283 in children and adolescents with relapsed and refractory solid tumors.
Unspecified Childhood Solid Tumor, Protocol Specific
Drug: multikinase inhibitor AT9283
Other: enzyme-linked immunosorbent assay
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Other: pharmacological study
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A CCLG/Cancer Research UK Phase I Trial of AT9283 (a Selective Inhibitor of Aurora Kinases) Given for 72 Hours Every 21 Days Via Intravenous Infusion in Children and Adolescents With Relapsed and Refractory Solid Tumors|
- Dose-limiting toxicities [ Designated as safety issue: Yes ]
- Maximum-tolerated dose [ Designated as safety issue: Yes ]
- Pharmacokinetic parameters and the correlation between them and toxicity and/or efficacy [ Designated as safety issue: No ]
- The magnitude and duration of biomarkers (M30 and M65 ELISA) change after AT9283 administration [ Designated as safety issue: No ]
- Objective tumor response according to RECIST criteria [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
- To evaluate the safety and tolerability of Aurora kinase inhibitor AT9283 by characterizing the dose-limiting toxicities in children and adolescents with relapsed and refractory solid tumors.
- To determine the maximum-tolerated dose of this regimen in these patients.
- To determine the pharmacokinetic parameters of this regimen in these patients.
- To demonstrate the pharmacodynamic (PD) activity of this regimen in these patients by studying its effects in surrogate tissue.
- To assess preliminary evidence of activity of this regimen by using appropriate objective tumor measurements in these patients.
- To demonstrate the PD activity of this regimen in these patients by studying its effects in both surrogate and tumor tissue (skin punch, bone marrow, and tumor biopsies).
OUTLINE: This is a multicenter, dose-escalation study.
Patients receive Aurora kinase inhibitor AT9283 IV over 72 hours on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and skin tissue samples are collected at baseline and periodically during treatment for pharmacokinetic studies and pharmacodynamic and biomarker (M30, M65, pHH53, p53, PCNA and Ki67) analysis by IHC and ELISA assays.
After completion of study therapy, patients are followed up periodically.
Peer Reviewed and Funded or Endorsed by Cancer Research UK.
|Birmingham Children's Hospital|
|Birmingham, England, United Kingdom, B4 6NH|
|Leeds General Infirmary|
|Leeds, England, United Kingdom, LS9 7TF|
|Royal Manchester Children's Hospital|
|Manchester, England, United Kingdom, M27 4HA|
|Great North Children's Hospital, Royal Victoria Infirmary|
|Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP|
|Royal Marsden - Surrey|
|Sutton, England, United Kingdom, SM2 5PT|
|Principal Investigator:||Darren Hargrave, MD||Royal Marsden NHS Foundation Trust|