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
- 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
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
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.
Masking: Open Label, Primary Purpose: Treatment
Darren Hargrave, MD
Royal Marsden NHS Foundation Trust
United Kingdom: Medicines and Healthcare Products Regulatory Agency