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

• Status: Completed
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Duke University
• Collaborator: Novartis Pharmaceuticals
• Treatments: Hydroxyurea; Imatinib Mesylate

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