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

NCT00770471 | Completed Phase 1 FDA Drug

• 5 other identifiers: NABTT-0801 CDR0000616542U01CA062475ABTC-0801NABTT-0801ABBOTT-M10-190
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 11

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult gliosarcoma; adult giant cell glioblastoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of ABT-888 (Phase I)

  continous

• Overall survival (Phase II)

  continous

Secondary Outcomes (3)

• Toxicity (Phase I)

  continous

• Pharmacokinetics of ABT-888 (Phase I)

  continous

• Frequency of toxicity (Phase II)

  continous

Study Arms (1)

Dose Escalation

EXPERIMENTAL

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

Interventions

temozolomide DRUG

Dose Escalation

veliparib DRUG

Dose Escalation

DNA methylation analysis GENETIC

Dose Escalation

gene expression analysis GENETIC

Dose Escalation

mutation analysis GENETIC

Dose Escalation

proteomic profiling GENETIC

Dose Escalation

high performance liquid chromatography OTHER

Dose Escalation

immunoenzyme technique OTHER

Dose Escalation

laboratory biomarker analysis OTHER

Dose Escalation

mass spectrometry OTHER

Dose Escalation

pharmacogenomic studies OTHER

Dose Escalation

pharmacological study OTHER

Dose Escalation

adjuvant therapy PROCEDURE

Dose Escalation

radiation therapy RADIATION

Dose Escalation

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) * Newly diagnosed disease * Patients enrolled in the phase I initial safety portion of the study must meet the following additional criteria: * Received 90% of planned radiotherapy and ≥ 80% of planned concurrent temozolomide within the past 28-49 days * No grade 3-4 toxicity attributed to temozolomide * Has undergone gadolinium MRI or contrast CT scan within the past 28 days * Patients enrolled in the phase I dose-escalation/phase II portion of the study must meet the following additional criteria: * Recovered from immediate post-operative period and maintained on a stable corticosteroid regimen (no increase in 5 days) prior to starting study treatment * Has undergone gadolinium MRI or contrast CT scan within the past 14 days PATIENT CHARACTERISTICS: * Karnofsky performance status 60-100% * Life expectancy ≥ 3 months * ANC ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Hemoglobin ≥ 9.0 g/dL * Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min * Total bilirubin ≤ 1.5 mg/dL * Transaminases ≤ 2.5 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception prior to, during, and for 3 months after completion of study therapy * Mini Mental State Exam score ≥ 15 * Able to swallow and retain oral medications * No concurrent serious infection or medical illness that would jeopardize the ability of the patient to receive study treatment with reasonable safety * No other malignancy within the past 5 years except for curatively treated carcinoma in situ or basal cell carcinoma of the skin * No known uncontrolled seizure disorder (i.e., status epilepticus) or seizures occurring ≥ 3 times per week over the past month PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 10 days since prior cytochrome P450-inducing anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, primidone, or oxcarbazepine) * At least 1 week since prior biopsy or resection of tumor (for patients enrolled in the phase I dose-escalation/phase II portion of the study) * No prior radiotherapy, chemotherapy, immunotherapy, hormonal therapy, or biological therapy (including immunotoxins, immunoconjugates, antisense therapy, peptide receptor antagonists, interferons, interleukins, tumor-infiltrating lymphocytes, lymphokine-activated killer cells, or gene therapy) for treatment of brain tumor (for patients enrolled in the phase I dose-escalation/phase II portion of the study) * Prior glucocorticoid therapy allowed * No other prior chemotherapy or investigational agents (for patients enrolled in the phase I initial safety portion of the study) * Prior Gliadel wafers allowed (for patients enrolled in the phase I portion of the study) * No prior Gliadel wafers (for patients enrolled in the phase II portion of the study)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (11)

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35294-3410, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157-1096, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104-4283, United States

Location

UPMC Cancer Centers

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Temozolomide; veliparib; DNA Methylation; Gene Expression Profiling; Chromatography, High Pressure Liquid; Immunoenzyme Techniques; Mass Spectrometry; Pharmacogenomic Testing; Chemotherapy, Adjuvant; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Genetic Techniques; Investigative Techniques; Chromatography, Liquid; Chromatography; Chemistry Techniques, Analytical; Immunoassay; Immunologic Techniques; Immunohistochemistry; Molecular Probe Techniques; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services; Combined Modality Therapy; Therapeutics; Drug Therapy

Study Officials

• Larry Kleinberg, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2008
• First Posted: October 10, 2008
• Study Start: July 13, 2009
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: June 27, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)