Clinical Trial Finder

Inclusion Criteria:

• - Pts have histologically confirmed diagnosis of recurrent/progressive WHO gr III & IV MG & meet following

  inclusion criteria:

  - Age >18 yrs.

• - Interval of >4 wks since prior surgery.

• - Interval of >4 wks since prior external beam radiation therapy (XRT) or chemo, unless there is unequivocal evidence of progressive disease & pts have recovered from all anticipated toxicity of most recent therapy.

• - Karnofsky performance status score >60.

• - Hematocrit > 29 percent, absolute neutrophil count (ANC) >1,500 cells/microliter, platelets >100,000 cells/microliter.

• - Serum creatinine <.

5mg/dl, blood urea nitrogen (BUN) <25 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) & bilirubin <1.5 x upper limit of normal (ULN)

• - For pts on corticosteroids, they have been on stable dose for 1 wk prior to entry.

• - Pts have had prior bevacizumab are eligible however interval of >6 wks must have elapsed since their last dose.

• - Signed informed consent approved by Institutional Review Board (IRB) prior to patient entry; - If sexually active, pts must agree to take contraceptive measures for duration of treatments.

Exclusion Criteria:

• - Prior therapy w either bevacizumab/EGFR-directed agents.

• - >3 prior recurrences.

• - Pregnancy/breast feeding.

• - Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil.

• - Evidence of central nervous system (CNS) hemorrhage on baseline MRI on CT scan.

• - Pts who require therapeutic anti-coagulation.

• - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics & psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state.

• - Pts w another primary malignancy that has required treatment within past year.

- Pts w acute/chronic renal insufficiency/those w acute renal insufficiency of any severity due to hepato-renal syndrome/in peri-operative liver transplantation period

Exploratory, Phase II study designed to assess anti-tumor activity of combinatorial regimen consisting of erlotinib + bevacizumab among pts w recurrent malignant glioma. Signal transduction inhibitors, such as erlotinib, as well as anti-angiogenic agents, such as bevacizumab, are expected to exert a cytostatic anti-tumor effect. Primary endpoint of study is probability of progression-free survival at 6 months. An important secondary objective is to further assess the safety of erlotinib + bevacizumab for pts w RMG. Pharmacokinetic studies included in protocol will evaluate impact of enzyme-inducing anti-epileptic drugs (EIAEDs) on metabolism of erlotinib. If study demonstrates that combo regimen of erlotinib + bevacizumab is associated w encouraging anti-tumor activity among pts w recurrent malignant glioma (RMG), further assessment of regimen in additional ph II & possibly ph III studies, will be considered.

Arms

Experimental: Bevacizumab + Erlotinib

Bevacizumab + Erlotinib

Interventions

Drug: - Bevacizumab and Erlotinib

Bevacizumab administered intravenously at dose 10 mg/kg every 2 wks. Erlotinib administered orally, continuously once daily in fasting state for each 42-day cycle. Dose of erlotinib is based on prior erlotinib monotherapy trial in RMG. It will be 200 mg/day for pts not on cytochrome P450 3A4 (CYP3A4)-enzyme inducing anti-epileptic drugs & 500 mg/day for pts on EIAEDs. It is possible that taking erlotinib w regular medications or supplements may change how erlotinib, subject's regular medications, or subject's regular supplements work. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent.