NCT00946335

ABT-888 and Temozolomide in Treating Young Patients With Recurrent or Refractory CNS Tumors

A Phase I Study of ABT-888, an Oral Inhibitor of Poly (ADP-Ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of ABT-888 when given in combination with temozolomide in treating young patients with recurrent or refractory CNS tumors. ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving ABT-888 together with temozolomide may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors. II. To study the plasma pharmacokinetics (PK) of ABT-888 and PARP inhibition in peripheral blood mononuclear cells (PBMC) in order to recommend a Phase 2 dose of ABT-888 in combination with temozolomide in children with recurrent or refractory CNS tumors. III. To describe the toxicities of the combination of ABT-888 and temozolomide in children with recurrent or refractory CNS tumors. SECONDARY OBJECTIVES: I. To measure non-homologous end-joining (NHEJ) activity in peripheral blood mononuclear cells (PBMC) prior to and following ABT-888 administration. II. To assess PARP expression and/or activity in tumor tissue obtained at either initial diagnosis or relapse. III. To determine expression and/or activity of DNA repair pathways, including MGMT and mismatch repair, in tumor tissues, when available. IV. To document, within the confines of this phase 1 trial, radiographic tumor response to ABT-888 and temozolomide. OUTLINE: This is a dose-escalation study of ABT-888. Patients receive oral ABT-888 twice daily and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for 13-26 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected for pharmacokinetics and further laboratory analysis.

Conditions

• Childhood Atypical Teratoid/Rhabdoid Tumor
• Childhood Central Nervous System Germ Cell Tumor
• Childhood Choroid Plexus Tumor
• Childhood Craniopharyngioma
• Childhood Ependymoblastoma
• Childhood Grade I Meningioma
• Childhood Grade II Meningioma
• Childhood Grade III Meningioma
• Childhood High-grade Cerebellar Astrocytoma
• Childhood High-grade Cerebral Astrocytoma
• Childhood Infratentorial Ependymoma
• Childhood Low-grade Cerebellar Astrocytoma
• Childhood Low-grade Cerebral Astrocytoma
• Childhood Medulloepithelioma
• Childhood Mixed Glioma
• Childhood Oligodendroglioma
• Childhood Supratentorial Ependymoma
• Recurrent Childhood Brain Stem Glioma
• Recurrent Childhood Brain Tumor
• Recurrent Childhood Cerebellar Astrocytoma
• Recurrent Childhood Cerebral Astrocytoma
• Recurrent Childhood Ependymoma
• Recurrent Childhood Medulloblastoma
• Recurrent Childhood Pineoblastoma
• Recurrent Childhood Spinal Cord Neoplasm
• Recurrent Childhood Subependymal Giant Cell Astrocytoma
• Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor
• Recurrent Childhood Visual Pathway and Hypothalamic Glioma

Interventions

Type	Name	Description
DRUG	veliparib	Given PO
DRUG	temozolomide	Given PO
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2009-07-01
• Primary completion: 2011-10-01
• Completion: 2014-06-01
• First posted: 2009-07-27
• Last updated: 2014-07-09

Locations

1 site across 1 country: United States