Clinical trial NCT00671970: Phase (Ph) II Bevacizumab + Erlotinib for Patients (Pts) With Recurrent Malignant Glioma (MG)
Official title: Phase II Trial of Bevacizumab Plus Erlotinib for Patients With Recurrent Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma
Gliosarcoma
Keywords: Glioblastoma
Gliosarcoma
Recurrent MG
Malignant glioma
Glioma
Glioblastoma multiforme (GBM)
GBM
Brain tumor
Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic oligoastrocytoma
Bevacizumab
Avastin
Erlotinib
Tarceva
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2008-05-06
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed description: 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

Primary outcomes:
measure: 6 Month Progression-free Survival
timeFrame: 6 months
Secondary outcomes:
measure: Radiographic Response
timeFrame: Patients were followed for the duration of the study, with a median follow-up of 103 weeks for grade III participants and 141.8 weeks for grade IV participants
measure: Pharmacokinetics of Erlotinib: Cmax
timeFrame: Day 1 and 42 of Dosing Erlotinib
measure: Pharmacokinetics of Erlotinib: AUC
timeFrame: Day 1 and 42 of Dosing Erlotinib
measure: Association of Biomarkers and One-year Survival - Epidermal Growth Factor (EGFR)
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - EGFR vIII
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - Phosphatase and Tensin Homologue (PTEN)
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - Phosphorylated Protein Kinase B (pAKT)
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - Phosphorylated Mitogen-activated Protein Kinase (pMAPK)
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - Vascular Endothelial Growth Factor (VEGF)
timeFrame: 1 year
measure: Association of Biomarkers and One-year Survival - VEGFR-2
timeFrame: 1 year
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: David A. Reardon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sathornsumetee S, Desjardins A, Vredenburgh JJ, McLendon RE, Marcello J, Herndon JE, Mathe A, Hamilton M, Rich JN, Norfleet JA, Gururangan S, Friedman HS, Reardon DA. Phase II trial of bevacizumab and erlotinib in patients with recurrent malignant glioma. Neuro Oncol. 2010 Dec;12(12):1300-10. doi: 10.1093/neuonc/noq099. Epub 2010 Aug 17.