Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)

Primary objective:

To estimate 6-month progression free survival probability of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab.

Secondary Objectives:

To evaluate safety \& tolerability of erlotinib + bevacizumab among pts w recurrent malignant gliomas To evaluate radiographic response of pts w recurrent malignant gliomas treated w erlotinib + bevacizumab To evaluate pharmacokinetics of erlotinib when administered to pts w recurrent malignant gliomas; \& to examine relationship of clinical response to Epidermal Growth Factor (EGFR) expression, amplification, \& v-III mutation, phosphatase and tensin homolog (PTEN) expression, vascular endothelial growth factor (VEGF) expression, vascular endothelial growth factor receptor 2 (VEGFR-2) \& phosphorylated protein kinase B (PKB/Akt) in archival tumor samples

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.

Eligibility Criteria:
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