Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma

March 26, 2013 updated by: Duke University

A Phase I Study of Imatinib Mesylate in Combination With Temozolomide in Patients With Malignant Glioma

RATIONALE: Imatinib mesylate 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 imatinib mesylate together with temozolomide may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of imatinib mesylate when given together with temozolomide in treating patients with malignant glioma.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the maximum tolerated dose and dose-limiting toxicity, if attainable, of imatinib mesylate in combination with temozolomide in patients with malignant glioma.
  • Characterize the safety and tolerability of imatinib mesylate, including acute and chronic toxicities, in these patients.
  • Determine the effect of temozolomide on the pharmacokinetics (PK) of imatinib mesylate at each dose level.
  • Evaluate the impact of enzyme-inducing anti-epileptic drug (EIAED) coadministration on the PK of imatinib mesylate using a population-based PK approach.
  • Evaluate the antitumor activity of imatinib mesylate plus temozolomide.

OUTLINE: This is a dose-escalation study of imatinib mesylate. Patients are stratified according to concurrent enzyme-inducing anticonvulsants (e.g., phenytoin, phenobarbital, carbamazepine, fosphenytoin, primidone, oxcarbazepine) (yes vs no).

Patients receive oral imatinib mesylate once or twice daily on days 1-8 and oral temozolomide once daily on days 4-8. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of patients receive escalating doses of imatinib mesylate until the maximum tolerated dose is determined.

On days 1 and 8 of course 1, blood is drawn for pharmacokinetic studies.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

65

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed malignant glioma

    • Any of the following subtypes:

      • Glioblastoma multiforme
      • Gliosarcoma
      • Anaplastic astrocytoma
      • Anaplastic oligodendroglioma
      • Anaplastic oligoastrocytoma
    • Previous histologic diagnosis of a lower grade of glioma allowed if there is histologic evidence of progression to a diagnosis of malignant glioma
    • Multifocal disease allowed
  • Must have undergone prior conventional external-beam radiation therapy

  • Stable disease, disease recurrence, or relapsed disease

    • Must not have received any systemic therapy for this recurrence or relapse
    • No prior progressive disease
  • No central/systemic fluid collections (pericardial effusion, pulmonary effusion, ascites) ≥ grade 2
  • No evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative grade 1 hemorrhage

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Absolute neutrophil count > 1,500/mm³
  • Hemoglobin > 9 g/dL
  • Platelet count > 100,000/mm³
  • AST and ALT < 2.5 times upper limit of normal (ULN)
  • Bilirubin < 1.5 times ULN
  • Creatinine < 1.5 times ULN
  • No chronic renal disease
  • No active uncontrolled infection
  • No uncontrolled diabetes

  • No excessive risk of bleeding, as defined by occurrence of any of the following:

    • Stroke within the past 6 months
    • History of CNS or intraocular bleed
    • Septic endocarditis
  • No history of labile hypertension
  • No congestive heart failure
  • No poorly controlled hypertension
  • No myocardial infarction within the past 6 months
  • No history of poor compliance with antihypertensive regimen
  • No other severe and/or uncontrolled medical disease that would preclude study participation
  • No peripheral edema ≥ grade 2
  • No gastrointestinal bleeding
  • No gross hematuria
  • No other active systemic bleeding
  • Patients must not have experienced toxicity ≥ grade 3 with prior treatment with either temozolomide or imatinib mesylate
  • No other primary malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix or other cancer not currently clinically significant nor requiring active interventions

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Recovered from all prior therapy
  • Prior surgical resection(s) allowed
  • At least 2 weeks since prior surgery
  • At least 2 weeks since prior chemotherapy (6 weeks for nitrosoureas)
  • At least 2 weeks since prior external-beam radiotherapy
  • At least 2 weeks since prior investigational drugs
  • More than 1 week since prior biologic, immunotherapeutic, or cytostatic agents
  • No concurrent warfarin

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and tolerability
Maximum tolerated dose
Pharmacokinetics
Dose-limiting toxicity
Anti-tumor activity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2004

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

July 19, 2006

First Submitted That Met QC Criteria

July 19, 2006

First Posted (Estimate)

July 20, 2006

Study Record Updates

Last Update Posted (Estimate)

March 28, 2013

Last Update Submitted That Met QC Criteria

March 26, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00004364
  • DUMC-5514-06-1R2
  • NOVARTIS-DUMC-5514-06-1R2
  • CDR0000483760 (Other Identifier: NCI)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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