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

NCT00671970 | Completed Phase 2 Results

• 1 other identifier: Pro00000220
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 6 Month Progression-free Survival

  The proportion of patients alive and progression free at 6 months

  6 months

Secondary Outcomes (10)

• Radiographic Response

  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

• Pharmacokinetics of Erlotinib: Cmax

  Day 1 and 42 of Dosing Erlotinib

• Pharmacokinetics of Erlotinib: AUC

  Day 1 and 42 of Dosing Erlotinib

• Association of Biomarkers and One-year Survival - Epidermal Growth Factor (EGFR)

  1 year

• Association of Biomarkers and One-year Survival - EGFR vIII

  1 year

Study Arms (1)

Bevacizumab + Erlotinib

EXPERIMENTAL

Bevacizumab + Erlotinib

Drug: Bevacizumab and Erlotinib

Interventions

Bevacizumab and Erlotinib DRUG

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.

Also known as: Bevacizumab, Erlotitnib, Avastin, Tarceva

Bevacizumab + Erlotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  PMID: 20716591 DERIVED

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms; Astrocytoma; Oligodendroglioma

Interventions

Bevacizumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. David Reardon
• Organization: Dana Farber Cancer Institute

David_Reardon@DFCI.HARVARD.EDU

(617) 632-2166

Study Officials

• David A. Reardon, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: May 6, 2008
• Study Start: February 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: April 1, 2010
• Last Updated: May 13, 2013
• Results First Posted: May 13, 2013

Record last verified: 2013-03

Locations

US (1)