Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)

• Patients with grade II LGG that is recurrent/progressive following prior surgical resection while on non-decreasing dose of corticosteroids
• > 25percent enlargement of bidimensional measure/new lesions on sequential imaging new \&/or worsening neurologic deficits
• Patients with progressive/recurrent optic pathway tumors
• Patients have measurable disease on MRI/CT
• Interval of > 4 wks between prior external beam radiation therapy (XRT)/chemo,\& enrollment on protocol unless there is unequivocal evidence of tumor progression \& patient has recovered from all expected toxicities associated with prior therapy. Patients treated w chemo agents such as VP-16 who would normally be retreated after shorter intervals may be treated at usual starting time even if \< 4 wks from last prior dose of chemo
• Patients not have had tumor biopsy \< 1 wk/surgical resection \< 2 wks prior to starting study drug
• Patients enrolling on arm B must be on > 1 enzyme inducing anticonvulsants for >2 wks prior to starting study drug
• Patients should be on non-increasing dose of steroids for > 7 days prior to obtaining baseline Gd-MRI of brain
• Patients should be on non-increasing dose of steroids for > 7 days prior to starting study drug
• Multifocal disease is eligible
• Age > 18 yrs old
• Karnofsky Performance Status (KPS) of > 60
• absolute neutrophil count (ANC) > 1.5 x 10 9/L
• Hgb > 9 g/dL
• Platelets > 100 x 10 9/L
• K ≥ lower limit of normal (LLN)/correctable with supplements
• Ca ≥ LLN/correctable with supplements
• P ≥ LLN/correctable with supplements
• aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) \& Alanine transaminase (ALT)/ Serum Glutamic Pyruvate Transaminase (SGPT} \< 2.5 x ULN
• Serum bilirubin \< 1.5 x upper limit of normal (ULN)
• Serum creatinine \< 1.5 x ULN/measured 24hr Creatinine Clearance > 50 mL/min/1.73m2
• Life expectancy ≥ 12wks
• Written informed consent obtained prior to screening procedures

Exclusion Criteria:

• Prior progressive disease/toxicity grade ≥ 3 with prior hydroxyurea therapy
• Prior treatment with imatinib/other platelet derived growth factor (PDGF)-directed therapy
• Excessive risk of bleeding as defined by stroke \< 6 months, history of central nervous system (CNS)/intraocular bleed, or septic endocarditis
• Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for stable post-operative gr1 hemorrhage
• Pregnant/breast feeding, /adults of reproductive potential not employing effective method of birth control
• Concurrent severe and/or uncontrolled medical disease that could compromise participation in study
• Acute/chronic liver disease
• Confirmed diagnosis of HIV infection
• Impairment of GI function/GI disease that may significantly alter absorption of imatinib
• Patients taking Coumadin
• Patients have received investigational drugs \< 2wks prior to entry on study/have not recovered from toxic effects of such therapy
• Patients have received biologic, immunotherapeutic/cytostatic agents \< 1 wk prior to entry on study/have not recovered from toxic effects of such therapy
• Patient > 5 yrs free of another primary malignancy except: if other primary malignancy is not currently clinically significant/requiring active intervention, or if other primary malignancy is basal cell skin cancer/ cervical carcinoma in situ. Existence of any other malignant disease is not allowed
• Patients have had any surgery other than resection of brain tumor \< 2 wks prior to entry on study/have not recovered from side effects of such therapy
• Patients unwilling to/unable to comply with protocol
• Active systemic bleeding, such as GI bleeding/gross hematuria
• Gr2 /> peripheral edema/central/systemic fluid collections
• Patients who enroll on arm A must have not received any EIAC for > 2 wks prior to starting study regimen

• Any of following exclusion criteria to MRI imaging:

  • Cardiac pacemaker
  • Ferromagnetic metal implants other than those approved as safe for use in magnetic resonance (MR) scanners
  • Claustrophobia
  • Obesity