Overview

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