Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)
Condition: Glioblastoma; Gliosarcoma
MeSH terms: Glioblastoma; Glioma; Gliosarcoma
Intervention: Bevacizumab and Erlotinib
Intervention description: 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.
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Glioblastoma; Gliosarcoma; Recurrent MG; Malignant glioma; Glioma; Glioblastoma multiforme (GBM); GBM; Brain tumor; Anaplastic astrocytoma; Anaplastic oligodendroglioma; Anaplastic oligoastrocytoma; Bevacizumab; Avastin; Erlotinib; Tarceva

Summary:

      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
    

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