NCT00985868

AT9283 in Children and Adolescents With Relapsed and Refractory Solid Tumors

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 2 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

OBJECTIVES: Primary * 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. Secondary * 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. Tertiary * 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.If a patient is benefiting from treatment with AT9283 (i.e. has stable or responding disease as measured by RECIST) and the benefit risk balance is considered acceptable then further treatment may be given. 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.

Conditions

• Unspecified Childhood Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	multikinase inhibitor AT9283
OTHER	enzyme-linked immunosorbent assay
OTHER	immunohistochemistry staining method
OTHER	laboratory biomarker analysis
OTHER	pharmacological study

Timeline

• Start date: 2009-09-01
• Primary completion: 2016-01-25
• Completion: 2019-11-20
• First posted: 2009-09-29
• Last updated: 2019-11-29

Locations

5 sites across 1 country: United Kingdom