EGFR Inhibition Using Weekly Erlotinib for Recurrent Malignant Gliomas

• Status: Completed
• Trial end date: 2018-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Andrew B Lassman, MD; Andrew Lassman
• Collaborators: Genentech, Inc.; OSI Pharmaceuticals
• Treatments: Erlotinib Hydrochloride

Criteria

Inclusion Criteria:

• 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.

Cohort A (medical) specific inclusion criteria:

• Fulfill all of the general inclusion criteria.

• MRI/CT must demonstrate measurable enhancing tumor of at least 1cm2 in cross-sectional area to allow assessment of radiographic response, unless: measurable disease is not present because the patient underwent gross total resection as the most recent anti-tumor therapy.

• At least 3 months have elapsed between any prior brain radiotherapy and initiation of study therapy.

• MRI/CT must demonstrate measureable enhancing tumor at least 1cm by 1cm squared in cross-sectional area to allow assessment of radiographic response.

• Stable or decreasing dose of corticosteroids for a minimum of 5 days before the baseline MRI/CT.

• The baseline MRI/CT must be performed on the 14th day or less prior to initiation of study treatment.

Cohort B (surgical) specific inclusion criteria:

• Fulfill all of the general inclusion criteria.

• An MRI/CT scan showing progression is required.

Exclusion Criteria:

• 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.