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Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma

Primary Purpose

Brain and Central Nervous System Tumors

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
imatinib mesylate
temozolomide
pharmacological study
Sponsored by
Duke University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma, adult mixed glioma, adult anaplastic astrocytoma, recurrent adult brain tumor, adult glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Duke Cancer Institute

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 19, 2006
Last Updated
March 26, 2013
Sponsor
Duke University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00354068
Brief Title
Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma
Official Title
A Phase I Study of Imatinib Mesylate in Combination With Temozolomide in Patients With Malignant Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain and Central Nervous System Tumors
Keywords
adult anaplastic oligodendroglioma, adult giant cell glioblastoma, adult gliosarcoma, adult mixed glioma, adult anaplastic astrocytoma, recurrent adult brain tumor, adult glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
65 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
imatinib mesylate
Intervention Type
Drug
Intervention Name(s)
temozolomide
Intervention Type
Other
Intervention Name(s)
pharmacological study
Primary Outcome Measure Information:
Title
Maximum tolerated dose
Title
Dose-limiting toxicity
Title
Safety and tolerability
Title
Pharmacokinetics
Title
Anti-tumor activity

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David A. Reardon, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Duke Cancer Institute
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18359865
Citation
Reardon DA, Desjardins A, Vredenburgh JJ, Sathornsumetee S, Rich JN, Quinn JA, Lagattuta TF, Egorin MJ, Gururangan S, McLendon R, Herndon JE 2nd, Friedman AH, Salvado AJ, Friedman HS. Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: phase 1 trial in adults with malignant glioma. Neuro Oncol. 2008 Jun;10(3):330-40. doi: 10.1215/15228517-2008-003. Epub 2008 Mar 21.
Results Reference
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Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma

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