- To evaluate activity of imatinib mesylate and hydroxyurea among patients with
progressive/recurrent grade II low-grade glioma (LGG) as measured by 12-month
progression free survival
Secondary objectives:
- To evaluate progression-free survival (PFS), overall survival and objective response
rate among patients with progressive/recurrent grade II LGG treated with imatinib
mesylate plus hydroxyurea
- To assess safety and tolerability of imatinib mesylate + hydroxyurea in this population
Inclusion Criteria:
- 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
