Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma

NCT ID: NCT00354913

Last Updated: 2013-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-05-31
• Study Completion Date: 2010-10-31

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 hydroxyurea, 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 hydroxyurea may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with hydroxyurea works in treating patients with recurrent or progressive meningioma.

Detailed Description

OBJECTIVES:

Primary

• Evaluate the activity of imatinib mesylate and hydroxyurea, as measured by 6-month progression-free survival, in patients with recurrent or progressive meningioma.

Secondary

• Evaluate the progression-free survival (PFS)
• Overall survival (OS),
• Objective response rate among patients treated with this regimen.

OUTLINE: This is an open-label study.

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

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

Conditions

Glioblastoma; Gliosarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib mesylate+hydroxyurea

All patients receive imatinib mesylate and hydroxyurea orally on a daily, continuous basis. Dosing of imatinib mesylate is adjusted for patients who are also receiving p450-inducing anti-epileptic drugs.

Group Type: EXPERIMENTAL

hydroxyurea

Intervention Type: DRUG

Hydroxyurea is administered orally twice a day. The dose will be set at 500 mg twice a day for all patients. If vomiting occurs not additional trial medication should be taken that day in an effort to replace the material that has been vomited. It is recommended that patients take their prescribed hydroxyurea at the same time that they take their prescribed imatinib mesylate, however, a 30-60 minute interval between agents is acceptable, if required for practical or other compliance issues.

imatinib mesylate

Intervention Type: DRUG

Imatinib administered orally on daily, continuous basis. Imatinib doses of 400mg/600mg administered once daily, whereas daily doses of 800mg/greater administered as equally divided dose taken twice day.

Dose for Imatinib:

Patients receiving p450-inducing antiepileptic drugs:500mg twice day Patients not receiving p450-inducing antiepileptic drugs:400mg/day.

If patients who were not on Cytochrome P450, family 3, subfamily A (CYP3A) enzyme-reducing anti-epileptic drug (EIAED) when originally enrolled must initiate CYP3A enzyme-inducing anti-epileptic drug while on study, study regimen will remain same for minimum of 2 wks before pt transitions to dosing as specified for patients on anti-epileptic drug. If patients originally enrolled must discontinue all EIAEDs while on study, in interest of patient safety, dosing of study regimen will transition to that of patients not on anti-epileptics immediately.

Interventions

hydroxyurea

Hydroxyurea is administered orally twice a day. The dose will be set at 500 mg twice a day for all patients. If vomiting occurs not additional trial medication should be taken that day in an effort to replace the material that has been vomited. It is recommended that patients take their prescribed hydroxyurea at the same time that they take their prescribed imatinib mesylate, however, a 30-60 minute interval between agents is acceptable, if required for practical or other compliance issues.

Intervention Type: DRUG

imatinib mesylate

Imatinib administered orally on daily, continuous basis. Imatinib doses of 400mg/600mg administered once daily, whereas daily doses of 800mg/greater administered as equally divided dose taken twice day.

Dose for Imatinib:

Patients receiving p450-inducing antiepileptic drugs:500mg twice day Patients not receiving p450-inducing antiepileptic drugs:400mg/day.

If patients who were not on Cytochrome P450, family 3, subfamily A (CYP3A) enzyme-reducing anti-epileptic drug (EIAED) when originally enrolled must initiate CYP3A enzyme-inducing anti-epileptic drug while on study, study regimen will remain same for minimum of 2 wks before pt transitions to dosing as specified for patients on anti-epileptic drug. If patients originally enrolled must discontinue all EIAEDs while on study, in interest of patient safety, dosing of study regimen will transition to that of patients not on anti-epileptics immediately.

Intervention Type: DRUG

Other Intervention Names

Droxia; Hydrea; Hydroxycarbamide; Gleevec

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed meningioma
• Recurrent or progressive disease after prior surgical resection
• Measurable disease by contrast-enhanced MRI
• Multifocal disease allowed
• No evidence of intratumor hemorrhage on pretreatment diagnostic imaging

• Stable postoperative grade 1 hemorrhage allowed
• No peripheral edema or central or systemic fluid collections ≥ grade 2 (e.g., pericardial effusion, pulmonary effusion, ascites)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute neutrophil count > 1,500/mm³
• Hemoglobin > 9 g/dL
• Platelet count > 100,000/mm³
• Potassium normal*
• Calcium normal*
• Magnesium normal*
• Phosphorus normal*
• alanine aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 times upper limit of normal (ULN)
• Bilirubin < 1.5 times ULN
• Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No excessive risk of bleeding, as defined by stroke within the past 6 months
• No active systemic bleeding (i.e., gastrointestinal bleeding or gross hematuria)
• No history of central nervous system (CNS) or intraocular bleeding or septic endocarditis
• No concurrent severe and/or uncontrolled medical disease, including any of the following:

• Uncontrolled diabetes
• Congestive cardiac failure
• Myocardial infarction within the past 6 months
• Poorly controlled hypertension
• History of labile hypertension
• History of poor compliance with antihypertensive regimen
• Chronic renal disease
• Active uncontrolled infection requiring intravenous antibiotics
• No acute or chronic liver disease (i.e., hepatitis, cirrhosis)
• No HIV positivity
• No impairment of gastrointestinal function or disease that may significantly alter the absorption of imatinib mesylate, including any of the following:

• Ulcerative disease
• Uncontrolled nausea
• Vomiting
• Diarrhea
• Malabsorption syndrome
• Bowel obstruction
• Inability to swallow tablets
• No other malignancy within the past 5 years except basal cell skin cancer or cervical carcinoma in situ NOTE: *Unless correctable with supplements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from prior therapy
• More than 1 week since prior tumor biopsy
• More than 2 weeks since prior surgical resection
• Prior hydroxyurea allowed provided patient has not had progressive disease or toxicity > grade 3
• No prior imatinib mesylate or other platelet-derived growth factor-directed therapy
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)*

• Chemotherapeutic agents such as etoposide that are normally given at shorter intervals allowed even if < 4 weeks from last prior dose of chemotherapy
• At least 4 weeks since prior radiotherapy*
• At least 1 week since prior biological, immunotherapeutic, or cytostatic drugs
• At least 2 weeks since prior investigational drugs
• No concurrent warfarin NOTE: *Unless there is unequivocal evidence of tumor progression

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David A. Reardon, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

Duke Cancer Institute

Durham, North Carolina, United States

Countries

United States

References

Reardon DA, Norden AD, Desjardins A, Vredenburgh JJ, Herndon JE 2nd, Coan A, Sampson JH, Gururangan S, Peters KB, McLendon RE, Norfleet JA, Lipp ES, Drappatz J, Wen PY, Friedman HS. Phase II study of Gleevec(R) plus hydroxyurea (HU) in adults with progressive or recurrent meningioma. J Neurooncol. 2012 Jan;106(2):409-15. doi: 10.1007/s11060-011-0687-1. Epub 2011 Sep 22.

Reference Type: RESULT

PMID: 21938530 (View on PubMed)

Other Identifiers

DUMC-7082-05-4R0

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-DUMC-7082-05-4R0

Identifier Type: -

Identifier Source: secondary_id

Pro00006768

Identifier Type: -

Identifier Source: org_study_id

NCT00611234

Identifier Type: -

Identifier Source: nct_alias