A Phase II Study of Imatinib Mesylate Plus Hydroxyurea in the Treatment of Patients With Recurrent/Progressive Meningioma
Inclusion Criteria:
- Patients with confirmed meningioma that is recurrent/progressive following prior
surgical resection
- Patients have measurable disease on MRI using gadolinium-enhanced T1 sequences
- Interval of >4 wks between prior XRT/chemo, & enrollment on protocol unless there is
unequivocal evidence of tumor progression & pt has recovered from all expected
toxicities associated w prior therapy. However, 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 with tumor biopsy <1 week or surgical resection <2 weeks 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 > 18yrs old
- KPS of > 60
- Patients must have following laboratory values:
- Hematology:
- ANC > 1.5 x 10^9/L
- Hgb> 9 g/dL
- Platelets>100 x 10^9/L
- Biochemistry:
- K≥ LLN/correctable w supplement
- Total Ca ≥ LLN/correctable with supplement
- P ≥ LLN/correctable w supplement
- AST/SGOT & ALT/SGPT < 2.5 x ULN
- Serum bilirubin < 1.5 x ULN
- Serum creatinine ,1.5 x ULN/measured 24hr CrCl> 50 mL/min/1.73m2
- Life expectancy ≥ 12wks
- Written informed consent obtained prior to any screening procedures
Exclusion Criteria:
- Prior progressive disease/toxicity gr ≥3 w prior hydroxyurea therapy
- Prior treatment with imatinib/other PDGF-directed therapy
- Excessive risk of bleeding as defined by stroke<6 months, history of CNS/intraocular
bleed,septic endocarditis
- Evidence of intratumor hemorrhage on pretreatment diagnostic imaging, except for
stable post-operative gr1 hemorrhage
- Female patients who are 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 or GI disease that may significantly alter absorption of
imatinib
- Patients who are taking Coumadin
- Patients who have received investigational drugs <2wks prior to entry on this study
or who have not recovered from the toxic effects of such therapy
- Patients who have received biologic, immunotherapeutic or cytostatic agents within
1wk prior to entry on this study/who 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,/if
other primary malignancy is basal cell skin cancer/ cervical carcinoma in situ.
Existence of any other malignant disease is not allowed
- Patients who have had any surgery other than resection of brain tumor < 2 wks prior
to entry on this study/who 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
- Gr 2/greater peripheral edema/central/systemic fluid collections
- Patients who enroll on arm A must have not received any EIAC for at >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 MR
scanners
- Claustrophobia
- Obesity