Imatinib Mesylate and Hydroxyurea in Treating Patients With Recurrent or Progressive Meningioma
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Meningioma; Gliosarcoma
Intervention: hydroxyurea; imatinib mesylate
Intervention description: 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 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 MeSH terms: Imatinib Mesylate; Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: 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

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.
    

Eligibility 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