Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma
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| ClinicalTrials.gov Identifier: NCT00354913 |
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Recruitment Status :
Completed
First Posted : July 20, 2006
Results First Posted : January 14, 2013
Last Update Posted : January 18, 2013
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Glioblastoma Gliosarcoma | Drug: hydroxyurea Drug: imatinib mesylate | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 21 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent/Progressive Meningioma |
| Study Start Date : | May 2005 |
| Actual Primary Completion Date : | March 2009 |
| Actual Study Completion Date : | October 2010 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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.
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Drug: 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.
Other Names:
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. Other Name: Gleevec |
- Progression-free Survival at 6 Months [ Time Frame: From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months. For each participant, PFS was assessed at 6 months after treatment initiation. ]Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or death due to any cause.
- Median Progression-free Survival (PFS) [ Time Frame: From the date of study treatment initiation to the date of the first documented progression or death from any cause, whichever came first, assessed up to 69 months. ]Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
- Median Overall Survival (OS) [ Time Frame: From the date of study treatment initiation to the date of death from any cause, assessed up to 69 months. ]Time in months from the start of study treatment to date of death due to any cause. Patients alive at last follow-up are censored as of that follow-up date. Median OS was estimated using a Kaplan-Meier curve.
- Objective Response Rate [ Time Frame: 69 Months ]Percentage of participants with an objective response (complete response or partial response). Per modified Macdonald criteria and assessed by MRI, complete response (CR) was the disappearance of all target lesions and partial response (PR) was a ≥50% decrease in the sum of the longest diameter of target lesions. Objective response = CR+PR.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
- Histologically confirmed meningioma
- Recurrent or progressive disease after prior surgical resection
- Measurable disease by contrast-enhanced MRI
- Multifocal disease allowed
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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
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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
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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
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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
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): NCT00354913
| United States, North Carolina | |
| Duke Cancer Institute | |
| Durham, North Carolina, United States, 27710 | |
| Principal Investigator: | David A. Reardon, MD | Duke Cancer Institute |
Publications of Results:
| Responsible Party: | Duke University |
| ClinicalTrials.gov Identifier: | NCT00354913 History of Changes |
| Obsolete Identifiers: | NCT00611234 |
| Other Study ID Numbers: |
Pro00006768 DUMC-7082-05-4R0 NOVARTIS-DUMC-7082-05-4R0 |
| First Posted: | July 20, 2006 Key Record Dates |
| Results First Posted: | January 14, 2013 |
| Last Update Posted: | January 18, 2013 |
| Last Verified: | December 2012 |
Keywords provided by Duke University:
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adult grade I meningioma adult grade II meningioma adult grade III meningioma adult papillary meningioma adult anaplastic meningioma recurrent adult brain tumor glioblastoma multiforme (GBM) Imatinib |
Imatinib mesylate Hydroxyurea Droxia Hydrea Hydroxycarbamide Gleevec Meningioma |
Additional relevant MeSH terms:
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Glioblastoma Gliosarcoma Meningioma Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Vascular Tissue Meningeal Neoplasms |
Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Nervous System Diseases Imatinib Mesylate Hydroxyurea Anticonvulsants Antineoplastic Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antisickling Agents Nucleic Acid Synthesis Inhibitors |