ABT-888, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase 1

Completed

• Conditions: Brain and Central Nervous System Tumors
• Interventions: Drug: temozolomide; Drug: veliparib; Genetic: DNA methylation analysis; Genetic: gene expression analysis; Genetic: mutation analysis; Genetic: proteomic profiling; Other: high performance liquid chromatography; Other: immunoenzyme technique; Other: laboratory biomarker analysis; Other: mass spectrometry; Other: pharmacogenomic studies; Other: pharmacological study; Procedure: adjuvant therapy; Radiation: radiation therapy

• Registration Number: NCT00770471
• Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary

RATIONALE: ABT-888 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high-energy x-rays to kill tumor cells. 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 radiation therapy and temozolomide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of ABT-888 when given together with radiation therapy and temozolomide and to see how well it works in treating patients with newly diagnosed glioblastoma multiforme.

Detailed Description

OBJECTIVES:

Primary

* To determine the maximum tolerated dose (MTD) of ABT-888 when administered in combination with radiotherapy and temozolomide in patients with newly diagnosed glioblastoma multiforme. (Phase I)

* To estimate the overall survival of patients treated with ABT-888 when administered at the MTD in combination with radiotherapy and temozolomide. (Phase II)

Secondary

* To assess the toxicity associated with this regimen. (Phase I)

* To assess and describe the pharmacokinetics of ABT-888. (Phase I)

* To estimate the frequency of toxicity associated with this regimen. (Phase II)

OUTLINE: This is a multicenter, phase I dose-escalation study of ABT-888 followed by a phase II study.

* Initiation therapy: Patients receive oral ABT-888 twice daily (once on day 1 only) and oral temozolomide once daily (beginning on day 2) in weeks 1-6. Patients enrolled in the phase I dose-escalation/phase II portion of the study also undergo concurrent radiotherapy once daily 5 days a week (beginning on day 2) in weeks 1-6. Treatment continues in the absence of disease progression or unacceptable toxicity.

* Maintenance therapy: Beginning 4 weeks after completion of initiation therapy, patients receive oral ABT-888 twice daily on days 1-7 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 4 courses (6 courses for patients enrolled in the phase I dose-escalation/phase II portion of the study) in the absence of disease progression or unacceptable toxicity.

Blood samples are collected periodically for pharmacokinetic, pharmacogenetic, and pharmacodynamic analysis. Samples are analyzed for concentration of ABT-888 in plasma by reversed-phase isocratic high performance liquid chromatography with electrospray ionization mass spectrometry; identification of novel markers of treatment response by plasma proteomic evaluation; DNA methylation and/or mutation; and PARP inhibition by ELISA.

After completion of study therapy, patients are followed every 2 months.

Study Timeline

• Study First Submitted: 2008-10-09
• Study First Submitted QC: 2008-10-09
• Study First Posted: 2008-10-10
• Study Start: 2009-07-13
• Primary Completion: 2012-03-01
• Study Completion: 2012-03-01
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-25
• Last Update Posted: 2018-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dose Escalation	temozolomide	-
Dose Escalation	DNA methylation analysis	-
Dose Escalation	gene expression analysis	-
Dose Escalation	mutation analysis	-
Dose Escalation	proteomic profiling	-
Dose Escalation	high performance liquid chromatography	-
Dose Escalation	immunoenzyme technique	-
Dose Escalation	laboratory biomarker analysis	-
Dose Escalation	mass spectrometry	-
Dose Escalation	pharmacogenomic studies	-
Dose Escalation	pharmacological study	-
Dose Escalation	adjuvant therapy	-
Dose Escalation	radiation therapy	-
Dose Escalation	veliparib	-

Primary Outcome Measures

Name	Time	Method
Overall survival (Phase II)	continous
Maximum tolerated dose of ABT-888 (Phase I)	continous

Secondary Outcome Measures

Name	Time	Method
Frequency of toxicity (Phase II)	continous
Toxicity (Phase I)	continous
Pharmacokinetics of ABT-888 (Phase I)	continous

Trial Locations

Locations (11)

University of Wisconsin Comprehensive Cancer Center; 🇺🇸 Madison, Wisconsin, United States

Winship Cancer Institute of Emory University; 🇺🇸 Atlanta, Georgia, United States

Josephine Ford Cancer Center at Henry Ford Hospital; 🇺🇸 Detroit, Michigan, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States

Cleveland Clinic Taussig Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Abramson Cancer Center of the University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

UAB Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

UCSF Helen Diller Family Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

UPMC Cancer Centers; 🇺🇸 Pittsburgh, Pennsylvania, United States

Wake Forest University Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States