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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00770471
First received: October 9, 2008
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Temozolomide and ABT-888 in Subjects With Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of ABT-888 (Phase I) [ Time Frame: continous ] [ Designated as safety issue: Yes ]
  • Overall survival (Phase II) [ Time Frame: continous ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity (Phase I) [ Time Frame: continous ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics of ABT-888 (Phase I) [ Time Frame: continous ] [ Designated as safety issue: No ]
  • Frequency of toxicity (Phase II) [ Time Frame: continous ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: June 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00770471

Locations
United States, Alabama
UAB Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294-3410
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Michigan
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, United States, 48202
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
UPMC Cancer Centers
Pittsburgh, Pennsylvania, United States, 15232
United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Larry Kleinberg, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00770471     History of Changes
Other Study ID Numbers: NABTT-0801 CDR0000616542, U01CA062475, ABTC-0801, NABTT-0801, ABBOTT-M10-190
Study First Received: October 9, 2008
Last Updated: May 1, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult glioblastoma
adult gliosarcoma
adult giant cell glioblastoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014