Glioblastoma MultiformePhase 1/2NCT00301418
Oral Tarceva Study for Recurrent/Residual Glioblastoma Multiforme and Anaplastic Astrocytoma
A Phase 1/2 study testing Erlotinib in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Northwell Health at 1 site in United States.
Trial summary
This study will offer a safe treatment for patients with relapsing recurring glioblastoma (GBM) or anaplastic astrocytoma (AA). The trial will test the hypothesis that Erlotinib (Tarceva, OSI-774) can be safely used up to a dose of 150 mg two times a day for 12 months to ultimately enhance survival of patients with… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- What is being tested?
- Erlotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2006to May 2014
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male or female patients of ≥ 18 years of age.
- Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA). All patients will have samples of their tissue evaluated for EGFRvIII overexpression and PTEN loss.
- Patients with a histologically confirmed low grade brain tumor who relapse with an enhancing tumor on magnetic resonance imaging (MRI) can be evaluated for toxicity only.
- Patients must have at least one confirmed and evaluable tumor site.*
- A confirmed tumor site is one which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or computed tomography [CT] scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.
- Patients must have a Karnofsky performance status ≥ 60% (or the equivalent Eastern Cooperative Oncology Group [ECOG] level of 0-2) and an expected survival of ≥ three months.
Show all 19Show fewer
- No chemotherapy for six weeks prior to treatment under this research protocol and no external beam radiation for eight weeks prior to treatment under this research protocol.
- Patients must have adequate hematologic reserve with WBC ≥ 3000/mm3, absolute neutrophils ≥ 1500/mm3 and platelets ≥ 100,000/mm3. Patients who are on Coumadin must have a platelet count of ≥ 150,000/mm3
- Pre-enrollment chemistry parameters must show: bilirubin < 1.5X the institutional upper limit of normal (IUNL); AST or ALT < 2.5X IUNL and creatinine < 1.5X IUNL.
- Pre-enrollment coagulation parameters (PT and PTT) must be ≤ 1.5X the IUNL.
- Concomitant Medications:
- Growth factor(s): Must not have received within 1 week of entry onto this study.
- Steroids: Systemic corticosteroid therapy is permissible in patients with centrail nervous system (CNS) tumors for treatment of increased intracranial pressure or symptomatic tumor edema. Patients with CNS tumors who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to study entry.
- Study Specific: Patients on enzyme-inducing anticonvulsants will be changed to non-enzyme inducing anticonvulsants or will not be allowed on this study. Patients receiving proton pump inhibitor or H2 blockers will not be allowed on study. Patients taking antacids will be allowed on study although they should not take the antacid for two hours before or two hours after taking erlotinib.
- Patients must agree to use a medically effective method of contraception during and for a period of three months after the treatment period. A pregnancy test will be performed on each premenopausal female of childbearing potential immediately prior to entry into the research study.
- Patients should not have received a CYP3A4 inhibitor within 1 week of study entry and should not have received a CYP3A4 inducer within 4 weeks of study entry.
- Patients should not have received proton-pump inhibitors within 5 days of study entry or H2 blockers within 2 days of study entry.
- Patients on steroids must receive prophylaxis for Pneumocystis carinii pneumonia (PCP) with Bactrim, unless they have a history of allergy to sulfa drugs.
- Patients must be able to understand and give written informed consent. Informed consent must be obtained at the time of patient screening.
Who cannot join
- Previous treatment with Tarceva®.
- Women who are pregnant or lactating.
- Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.
- Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lenox Hill Brain Tumor Center
New York, New York, 10075
About this study
Official title: Phase I/II Trial of Oral Erlotinib (Tarceva, OSI-774) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma
This study will offer a safe treatment for patients with relapsing recurring glioblastoma (GBM) or anaplastic astrocytoma (AA). The trial will test the hypothesis that Erlotinib (Tarceva, OSI-774) can be safely used up to a dose of 150 mg two times a day for 12 months to ultimately enhance survival of patients with relapsed/refractory GBM/AA. Correlation of response to Tarceva with particular genetic alterations including epidermal growth factor receptor variant type III (EGFRvIII) amplification and phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) loss will be studied.
Read the detailed description
The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA, from initial diagnosis, despite multimodal treatment approaches. Initial therapy consists of either surgical resection, external beam radiation or both. The role of adjuvant or concomitant chemotherapy in the initial therapy of GBM and AA has not, as yet, been clearly defined. Since most of these patients experience a recurrence after first-line therapy, improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. In August 2003, the U.S. Food and Drug Administration (FDA) granted orphan drug status for Erlotinib in patients with malignant glioma. Erlotinib (OSI-774) has been shown to be active in a range of tumors including GBM, AA and non small cell lung cancer. Because of the promising results in preliminary studies of Erlotinib and because of significant experience with the safety of the dosages proposed in this study, this study will offer a safe adjuvant treatment for patients with relapsing recurring glioblastoma or anaplastic astrocytoma. Therefore, this phase I/II clinical research trial will test the hypothesis that Erlotinib can be safely used up to a dose of 150 mg bid for 12 cycles to ultimately enhance survival of patients with relapsed/refractory GBM/AA with particular genetic alterations including EGFRvIII amplification and PTEN loss.
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- Being tested
- Erlotinib
- Keywords
- Glioblastoma Multiforme, Anaplastic Astrocytoma, High Grade Glial Neoplasms, Brain Tumor
- Medical subject headings
- Glioblastoma, Astrocytoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErlotinibDrug
Also called Tarceva, OSI-774
Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol.
| Study group | Role | What they receive |
|---|---|---|
| Tarceva (Erlotinib) | Experimental | Not described Receives: Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Twice a Day Oral 150 mg Erlotinib Dosing
Greater than or equal to Grade 2 Adverse Event
Measured: duration of the trial
Secondary outcomes (2)
6-month Progression Free Survival (PFS)
Measured: Duration of the trial
Overall Survival (OS)
Measured: Duration of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2006 (estimated)
- Study startMar 2006
- Primary completionMay 2014
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Northwell HealthThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwell Health
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, John A. Boockvar, Northwell Health
- Investigators
- John A Boockvar, M.D., Principal investigator, Feinstein Institute for Medical Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00301418
- Sponsor's protocol ID
- 501007705
- Status last verified
- Jan 2016
- First submitted
- 9 Mar 2006
- Last updated
- 10 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005 Nov 10;353(19):2012-24. doi: 10.1056/NEJMoa051918.
PubMed 16282176
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Oral Erlotinib (Tarceva, OSI-774) for Treatment of Relapsed/Refractory Glioblastoma Multiforme and Anaplastic Astrocytoma
- ClinicalTrials.gov ID
- NCT00301418
- Acronym / sponsor ID
- 501007705
- Conditions
- Glioblastoma Multiforme, Anaplastic Astrocytoma
- Keywords
- Glioblastoma Multiforme, Anaplastic Astrocytoma, High Grade Glial Neoplasms, Brain Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Northwell HealthUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Mar 2006
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 10 Mar 2006 (estimated)
- Results
- Posted 10 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will offer a safe treatment for patients with relapsing recurring glioblastoma (GBM) or anaplastic astrocytoma (AA). The trial will test the hypothesis that Erlotinib (Tarceva, OSI-774) can be safely used up to a dose of 150 mg two times a day for 12 months to ultimately enhance survival of patients with relapsed/refractory GBM/AA. Correlation of response to Tarceva with particular genetic alterations including epidermal growth factor receptor variant type III (EGFRvIII) amplification and phosphatase and tensin homolog (mutated in multiple advanced cancers 1) (PTEN) loss will be studied.
Detailed description
The high-grade malignant brain tumors, glioblastoma multiforme (GBM) and anaplastic astrocytoma (AA), comprise the majority of all primary brain tumors in adults. This group of tumors also exhibits the most aggressive behavior, resulting in median overall survival durations of only 9-12 months for GBM, and 3-4 years for AA, from initial diagnosis, despite multimodal treatment approaches. Initial therapy consists of either surgical resection, external beam radiation or both. The role of adjuvant or concomitant chemotherapy in the initial therapy of GBM and AA has not, as yet, been clearly defined. Since most of these patients experience a recurrence after first-line therapy, improvements in both first-line and salvage therapy are critical to enhancing quality-of-life and prolonging survival. In August 2003, the U.S. Food and Drug Administration (FDA) granted orphan drug status for Erlotinib in patients with malignant glioma. Erlotinib (OSI-774) has been shown to be active in a range of tumors including GBM, AA and non small cell lung cancer. Because of the promising results in preliminary studies of Erlotinib and because of significant experience with the safety of the dosages proposed in this study, this study will offer a safe adjuvant treatment for patients with relapsing recurring glioblastoma or anaplastic astrocytoma. Therefore, this phase I/II clinical research trial will test the hypothesis that Erlotinib can be safely used up to a dose of 150 mg bid for 12 cycles to ultimately enhance survival of patients with relapsed/refractory GBM/AA with particular genetic alterations including EGFRvIII amplification and PTEN loss.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tarceva (Erlotinib) | Experimental | Drug: Erlotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Male or female patients of ≥ 18 years of age.
- Patients with a documented histologic diagnosis of relapsed or refractory glioblastoma multiforme (GBM), anaplastic astrocytoma (AA) or anaplastic mixed oligoastrocytoma (AOA). All patients will have samples of their tissue evaluated for EGFRvIII overexpression and PTEN loss.
- Patients with a histologically confirmed low grade brain tumor who relapse with an enhancing tumor on magnetic resonance imaging (MRI) can be evaluated for toxicity only.
- Patients must have at least one confirmed and evaluable tumor site.*
- A confirmed tumor site is one which is biopsy-proven. NOTE: Radiographic procedures (e.g., Gd-enhanced MRI or computed tomography [CT] scans) documenting existing lesions must have been performed within three weeks of treatment on this research study.
Key exclusion criteria (4 listed)
- Previous treatment with Tarceva®.
- Women who are pregnant or lactating.
- Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this research trial and will be advised that they must use effective contraception during and for a period of three months after the treatment period.
- Patients with significant intercurrent medical or psychiatric conditions that would place them at increased risk or affect their ability to receive or comply with treatment or post-treatment clinical monitoring.
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: Tarceva, OSI-774Tarceva®: Will be given at a starting dose of 150mg QD dose for the first cycle which is 28 days. This will be followed by 14 days of 100mg PO on a bid schedule and 150mg PO on a bid schedule for the final 14 days of the second cycle. Assuming no dose limiting toxicity, 150 mg PO tid will be continued for up to 10 more cycles. This is an outpatient regimen, in which the drug is admininistered orally. Tumor response will be assessed after every 2nd treatment cycle. Patients may receive a maximum of 12 cycles of treatment under this research protocol. | Drug | Tarceva (Erlotinib) |
Primary outcome
Safety of Twice a Day Oral 150 mg Erlotinib Dosing
Time frame: duration of the trial
Greater than or equal to Grade 2 Adverse Event
2 secondary outcomes
6-month Progression Free Survival (PFS)
Time frame: Duration of the trial
Overall Survival (OS)
Time frame: Duration of the trial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16282176Mellinghoff IK, Wang MY, Vivanco I, Haas-Kogan DA, Zhu S, Dia EQ, Lu KV, Yoshimoto K, Huang JH, Chute DJ, Riggs BL, Horvath S, Liau LM, Cavenee WK, Rao PN, Beroukhim R, Peck TC, Lee JC, Sellers WR, Stokoe D, Prados M, Cloughesy TF, Sawyers CL, Mischel PS. Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors. N Engl J Med. 2005 Nov 10;353(19):2012-24. doi: 10.1056/NEJMoa051918.
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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.
John A Boockvar, M.D. principal investigator
Feinstein Institute for Medical Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Erlotinib in people with Glioblastoma Multiforme and Anaplastic Astrocytoma, run by Northwell Health at 1 site 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 19 inclusion and 4 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 10 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety of Twice a Day Oral 150 mg Erlotinib Dosing (time frame: duration of the trial). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00301418, which also lists 1 linked publication.
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 10 Feb 2016.