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Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma

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ClinicalTrials.gov Identifier: NCT00354068
Recruitment Status : Completed
First Posted : July 20, 2006
Last Update Posted : March 28, 2013
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: imatinib mesylate Drug: temozolomide Other: pharmacological study Phase 1

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  (Clinical Trial)
Actual Enrollment : 65 participants
Primary Purpose: Treatment
Official Title: A Phase I Study of Imatinib Mesylate in Combination With Temozolomide in Patients With Malignant Glioma
Study Start Date : July 2004
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008





Primary Outcome Measures :
  1. Maximum tolerated dose
  2. Dose-limiting toxicity
  3. Safety and tolerability
  4. Pharmacokinetics
  5. Anti-tumor activity


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00354068


Locations
United States, North Carolina
Duke Cancer Institute
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
National Cancer Institute (NCI)
Investigators
Study Chair: David A. Reardon, MD Duke Cancer Institute

Publications of Results:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00354068     History of Changes
Other Study ID Numbers: Pro00004364
DUMC-5514-06-1R2
NOVARTIS-DUMC-5514-06-1R2
CDR0000483760 ( Other Identifier: NCI )
First Posted: July 20, 2006    Key Record Dates
Last Update Posted: March 28, 2013
Last Verified: March 2013

Keywords provided by Duke University:
adult anaplastic oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
adult mixed glioma
adult anaplastic astrocytoma
recurrent adult brain tumor
adult glioblastoma

Additional relevant MeSH terms:
Glioma
Nervous System Neoplasms
Central Nervous System Neoplasms
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
Imatinib Mesylate
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors