Phase II Imatinib + Hydroxyurea in Treatment of Patients With Recurrent/Progressive Grade II Low-Grade Glioma (LGG)
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Gliosarcoma
Intervention: Imatinib Mesylate & Hydroxyurea
Intervention description: Imatinib administered orally on daily. Imatinib is local irritant & must be taken in sitting position; mini of 2hrs should be allowed between last drug intake & going to bed. Imatinib doses 400mg/600mg administered once daily, whereas daily doses of 800mg/> administered as equally divided dose taken twice day. Dose for imatinib: Pts not receiving p450-inducing antiepileptic drugs: 400 mg/day. Pts receiving p450-inducing antiepileptic drugs: 500 mg twice day. It is recommended that pts take their prescribed imatinib mesylate at same time that they take their prescribed hydroxyurea, however, 30-60min interval between agents is acceptable if required for practical/other compliance issues.
Hydroxyurea administered orally twice day. Dosing will begin on day 1 of cycle 1 & continue daily. Drug is approximately 80 percent bioavailable. Dose will be 500mg twice day for all pts.
Intervention MeSH terms: Imatinib Mesylate; Hydroxyurea
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Glioblastoma; Gliosarcoma; glioblastoma multiforme (GBM); GBM; Imatinib Mesylate; Gleevec; Hydroxyurea; Droxia; Hydrea; Hydroxycarbamide; Imatinib; Brain tumor; Malignant brain tumor; Recurrent glioblastoma multiforme; Progressive glioblastoma multiforme

Summary:

      Primary objective:

        -  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
    

Eligibility criteria:

        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