EGFR Inhibition Using Weekly Erlotinib for Recurrent Malignant Gliomas

NCT01257594 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAJ7500
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to test the effectiveness of a drug called erlotinib in treating the tumor. This is a multi-center pilot study that explores efficacy and molecular effects of high dose weekly erlotinib for recurrent EGFR vIII mutant malignant gliomas, and correlate molecular profile of pre-treatment tissue with outcome.

Conditions

Brain Cancer

Keywords

Gliomas; Erlotinib; Glioblastoma; GBM; Gliosarcoma; Glioma

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (either radiographic response or at least 6 months of progression-free survival)

  All patients will have their tumor measurements recorded at baseline and at the time of each MRI/CT scan. Clinical efficacy of pulsatile dosing with the EGFR Tyrosine Kinase Inhibitor erlotinib in patient with EGFR vIII mutant, recurrent malignant gliomas will be explored by determination of radiographic response and 6 month progression-free survival (6mPFS rate).

  Up to 3 years

Study Arms (2)

No cytoreductive surgery planned

EXPERIMENTAL

Patients who are not candidates for surgery as part of their routine care will enroll into the medical arm of the trial. They will initiate pulsatile erlotinib dosing and continue therapy until either disease progression or intolerable toxicity.

Drug: erlotinib

Cytoreductive surgery planned

EXPERIMENTAL

Patients scheduled for "salvage" resection as part of their routine care will be considered for this cohort. They will receive 1 pre-operative dose of 2000 mg erlotinib. Resection will occur ≤ 3 hours after the pre-operative dose. After recovery from surgery, patients will resume pulsatile erlotinib dosing.

Drug: erlotinib; Procedure: Cytoreductive Surgery

Interventions

erlotinib DRUG

For patients with no cytoreductive surgery planned, patients will receive single-agent erlotinib at a starting dose of 2000 mg on days 1 of every 7 days. For patients with cytoreductive surgery planned, patients will receive single-agent erlotinib at a starting dose of 2000 mg day 1 of every 7 days (+/- 2 days). One pre-operative dose of 2000 mg erlotinib will be administered in an open-label, unblinded manner, administered in the hospital "on call" to the operating room.

Also known as: Tarceva

Cytoreductive surgery planned; No cytoreductive surgery planned

Cytoreductive Surgery PROCEDURE

Standard procedure

Cytoreductive surgery planned

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed intracranial malignant glioma of the following types: Glioblastoma (GBM), Gliosarcoma (GS), Anaplastic astrocytoma (AA), Anaplastic oligodendroglioma (AO), Anaplastic oligoastrocytoma (AOA, also called anaplastic mixed gliomas or AMG), High grade glioma not otherwise specified (NOS).
• EGFRvIII mutation detected on pretreatment tissue from at least 1 prior surgery.
• At least 15 unstained slides or at least 1 tissue blocks must be collected from at least one prior surgery.
• Recovered from toxic effects of prior therapies.
• Able to undergo contrast enhanced MRI scans (or CT scans for patients unable to tolerate MRI).
• Shown unequivocal evidence for contrast enhancing tumor progression by MRI (or CT for patients who cannot tolerate MRI) in comparison to a prior scan.
• Age \> or = 18 years.
• Karnofsky Performance Status \> or = 60%.
• Life expectancy of \> 8 weeks.
• Normal organ and marrow function, adequate liver function and adequate renal function before starting therapy.
• Women of child-bearing potential and men must agree to use adequate contraception.
• Women of childbearing potential must have a negative pregnancy test documented within 7 days prior to treatment.
• Women must agree not to breast feed.
• Ability to understand and the willingness to sign a written informed consent document.
• Ability to swallow the tablets.

You may not qualify if:

• Received prior treatment with convection enhanced delivery, other catheter based intratumoral treatment, or carmustine (BCNU)/Gliadel wafers.
• Prior therapy that included stereotactic radiosurgery during therapy for newly diagnosed or recurrent disease, or re-irradiation of any type, must have confirmation of true progressive disease rather than radiation necrosis based upon surgical documentation of recurrent/progressive disease.
• Prior treatment with an EGFR inhibitor.
• Received prior treatment with direct Vascular endothelial growth factor (VEGF)/Vascular Endothelial Growth Factor Receptors (VEGFR) inhibitors.
• Smoking or plan to smoke tobacco or marijuana during study therapy.
• Receiving any other investigational agents concurrently with study treatment.
• Taking Enzyme Inducing Anti-Epileptic Drug (EIAED). If previously on an EIAED, the patient must be off of it for at least two weeks prior to study treatment.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib.
• Uncontrolled intercurrent illness that would limit compliance with study requirements.
• Have HIV and are receiving combination antiretroviral therapy.
• Other active concurrent malignancy.

Sponsors & Collaborators

• Andrew B Lassman, MD: lead
• Genentech, Inc.: collaborator
• OSI Pharmaceuticals: collaborator

Study Sites (4)

Memorial Sloan-Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan-Kettering Cancer Center at Commack

Commack, New York, 11725, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center
• AAAJ7500

MeSH Terms

Conditions

Brain Neoplasms; Glioma; Glioblastoma; Gliosarcoma

Interventions

Erlotinib Hydrochloride; Cytoreduction Surgical Procedures

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Surgical Procedures, Operative

Study Officials

• Andrew Lassman, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: December 8, 2010
• First Posted: December 9, 2010
• Study Start: January 7, 2011
• Primary Completion: November 22, 2016
• Study Completion: December 31, 2018
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)