Imatinib Mesylate and Temozolomide in Treating Patients With Malignant Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00354068
• Other study ID #: Pro00004364
• Secondary ID: DUMC-5514-06-1R2
• Status: Completed
• Phase: Phase 1
• First received: July 19, 2006
• Last updated: March 26, 2013
• Start date: July 2004
• Est. completion date: November 2008

Study information

• Verified date: March 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• imatinib mesylate

• temozolomide

Other:
• pharmacological study

Locations

Country	Name	City	State
United States	Duke Cancer Institute	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 te — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose			Yes
Primary	Dose-limiting toxicity			Yes
Primary	Safety and tolerability			Yes
Primary	Pharmacokinetics			No
Primary	Anti-tumor activity			No