Brain CancerPhase 1NCT01257594
EGFR Inhibition Using Weekly Erlotinib for Recurrent Malignant Gliomas
A Phase 1 study testing erlotinib and Cytoreductive Surgery in people with Brain Cancer, run by Andrew B Lassman, MD at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Cancer
- What is being tested?
- erlotinib and Cytoreductive Surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 4 sitesUnited States
- Study dates
- 7 Jan 2011to 31 Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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 locations and contacts
4 sites in 1 country.
United States4 sites
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, 11725
Columbia University Irving Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Pilot Study of EGFR Inhibition Using High Dose Administration of Erlotinib Weekly for Recurrent Malignant Gliomas With EGFR Variant III Mutation
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.
Read the detailed description
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.
- Conditions
- Brain Cancer
- Being tested
- erlotinib, Cytoreductive Surgery
- Keywords
- Gliomas, Erlotinib, Glioblastoma, GBM, Gliosarcoma, Glioma
- Medical subject headings
- Brain Neoplasms, Glioma, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinibDrug
Also called Tarceva
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.
Cytoreductive SurgeryProcedure or surgery
Standard procedure
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: erlotinib; Procedure: Cytoreductive Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2010 (estimated)
- Study start7 Jan 2011
- Primary completion22 Nov 2016
- Study completion31 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Andrew B Lassman, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., OSI Pharmaceuticals
- Responsible party
- Sponsor-investigator, Andrew B Lassman, MD, Columbia University
- Investigators
- Andrew Lassman, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01257594
- Sponsor's protocol ID
- AAAJ7500
- Status last verified
- May 2023
- First submitted
- 8 Dec 2010
- Last updated
- 25 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of EGFR Inhibition Using High Dose Administration of Erlotinib Weekly for Recurrent Malignant Gliomas With EGFR Variant III Mutation
- ClinicalTrials.gov ID
- NCT01257594
- Acronym / sponsor ID
- AAAJ7500
- Conditions
- Brain Cancer
- Keywords
- Gliomas, Erlotinib, Glioblastoma, GBM, Gliosarcoma, Glioma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Andrew B Lassman, MDUniversity, hospital or other
- Collaborators
- Genentech, Inc., OSI Pharmaceuticals
- Study start
- 7 Jan 2011 (actual)
- Primary completion
- 22 Nov 2016 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 9 Dec 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| No cytoreductive surgery planned | Experimental | Drug: erlotinibPatients 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. |
| Cytoreductive surgery planned | Experimental | Drug: erlotinib, Procedure: Cytoreductive SurgeryPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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).
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| erlotinibAlso: TarcevaFor 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. | Drug | Cytoreductive surgery planned, No cytoreductive surgery planned |
| Cytoreductive SurgeryStandard procedure | Procedure or surgery | Cytoreductive surgery planned |
Primary outcome
Clinical Benefit Rate (either radiographic response or at least 6 months of progression-free survival)
Time frame: Up to 3 years
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2023.
- Memorial Sloan-Kettering Cancer CenterLink provided by the sponsor.
- AAAJ7500Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Lassman, MD principal investigator
Columbia University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib and Cytoreductive Surgery in people with Brain Cancer, run by Andrew B Lassman, MD at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Benefit Rate (either radiographic response or at least 6 months of progression-free survival) (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2023.