cropped color_logo_with_background.png

EGFR Inhibition Using Weekly Erlotinib for Recurrent Malignant Gliomas

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT01257594
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Andrew B Lassman, MD
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Andrew Lassman, MD
Principal Investigator Affiliation Columbia University
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other, Industry
Overall Status Completed
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain Cancer
Study Website: View Trial Website
Additional Details

This is a pilot study of erlotinib for subjects who have a brain tumor called a glioblastoma or another malignant glioma, which has continued to grow after treatment. The purpose of this study is to test the effectiveness of a drug called erlotinib in treating the tumor. The study drug, erlotinib (also called Tarceva) is a pill (taken by mouth) that has been approved by the U.S. Food and Drug Administration (FDA) for the subjects with other cancers (lung cancer or pancreatic cancer). It is not approved for glioblastoma or another malignant glioma. Erlotinib blocks a messenger that tells cancer cells to grow. That messenger is called Epidermal Growth Factor Receptor (EGFR). This type of tumor contains a form of EGFR called variant number 3 (abbreviated EGFR variant III or EGFRvIII for short) that is different from the normal form.Research suggests that erlotinib is particularly effective at stopping EGFRvIII. Research also suggests that high doses of erlotinib taken once per week may be more effective than low doses of erlotinib taken once per day.

Arms & Interventions

Arms

Experimental: No cytoreductive surgery planned

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.

Experimental: Cytoreductive surgery planned

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.

Interventions

Drug: - erlotinib

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.

Procedure: - Cytoreductive Surgery

Standard procedure

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Basking Ridge, New Jersey

Status

Address

Memorial Sloan-Kettering at Basking Ridge

Basking Ridge, New Jersey, 07920

Commack, New York

Status

Address

Memorial Sloan-Kettering Cancer Center at Commack

Commack, New York, 11725

New York, New York

Status

Address

Columbia University Irving Medical Center

New York, New York, 10032

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065