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

Sponsors and Collaborators:	Duke University Genentech
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00671970

Purpose

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 EGFR expression, amplification, & v-III mutation, PTEN expression, VEGF expression & phosphorylated PKB/Akt in archival tumor samples

Condition	Intervention	Phase
Glioblastoma Gliosarcoma	Drug: Bevacizumab and Erlotinib	Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Erlotinib Erlotinib hydrochloride Bevacizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Official Title:	Phase II Trial of Bevacizumab Plus Erlotinib for Patients With Recurrent Malignant Glioma

Further study details as provided by Duke University:

Primary Outcome Measures:

6 month progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

a. Radiographic response b. Pharmacokinetics of Erlotinib c. Correlation of clinical response & pathological findings of EGFR expression, amplification & EGFR-vIII expression, VEGF expression, PTEN expression & PKB/Akt expression [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Gr 3 or greater, treatment related, non-hematologic toxicities [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	56
Study Start Date:	February 2007
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Pts w recurrent GBM	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 CYP3A4-enzyme inducing anti-epileptic drugs & 650 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.
B: Experimental Pts w recurrent anaplastic glioma	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 CYP3A4-enzyme inducing anti-epileptic drugs & 650 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.

Arms

Assigned Interventions

A: Experimental

Pts w recurrent GBM

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 CYP3A4-enzyme inducing anti-epileptic drugs & 650 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.

B: Experimental

Pts w recurrent anaplastic glioma

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 CYP3A4-enzyme inducing anti-epileptic drugs & 650 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.

Detailed Description:

Exploratory, ph 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 EIAEDs on metabolism of erlotinib.

If study demonstrates that combo regimen of erlotinib + bevacizumab is associated w encouraging anti-tumor activity among pts w RMG, further assessment of regimen in additional ph II & possibly ph III studies, will be considered.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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, ANC >1,500 cells/microliter, platelets >100,000 cells/microliter
Serum creatinine <.5mg/dl, BUN <25 mg/dl, serum SGOT & bilirubin <1.5 x 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 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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671970

Contacts

Contact: David A. Reardon, MD	(919) 668-1409	david.reardon@duke.edu
Contact: KAREN Carter	(919) 668-2329	Karen.Carter@duke.edu

Locations

United States, North Carolina
Duke University Health System	Recruiting
Durham, North Carolina, United States, 27710
Contact: David A. Reardon, MD 919-668-1409 david.reardon@duke.edu
Contact: Raquel Newell (919) 681-3229 raquel.newell@duke.edu

Sponsors and Collaborators

Duke University

Genentech

Investigators

Principal Investigator:

David A. Reardon, MD

Duke University Health System

More Information

The Preston Robert Tisch Brain Tumor Center at DUKE This link exits the ClinicalTrials.gov site

Responsible Party:	Duke University Health System ( David A. Reardon, MD )
Study ID Numbers:	00000220
Study First Received:	January 29, 2008
Last Updated:	November 6, 2008
ClinicalTrials.gov Identifier:	NCT00671970
Health Authority:	United States: Food and Drug Administration

Keywords provided by Duke University:

Gliosarcoma
Glioblastoma
Recurrent MG
Malignant glioma
Glioma
GBM
Brain tumor

Anaplastic astrocytoma
Anaplastic oligodendroglioma
Anaplastic oligoastrocytoma
Bevacizumab
Avastin
Erlotinib
Tarceva

Study placed in the following topic categories:

Erlotinib
Glioblastoma
Astrocytoma
Bevacizumab
Recurrence
Brain Neoplasms
Neuroectodermal Tumors

Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Oligodendroglioma
Glioma
Gliosarcoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Enzyme Inhibitors
Angiogenesis Inhibitors

Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors
Neoplasms, Neuroepithelial

ClinicalTrials.gov processed this record on January 16, 2009