Brain and Central Nervous System TumorsPhase 1NCT00227032
Erlotinib in Treating Patients With Progressive Glioblastoma Multiforme
A Phase 1 study testing erlotinib hydrochloride in people with Brain and Central Nervous System Tumors, run by UNC Lineberger Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib in treating patients with progressive glioblastoma multiforme. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- erlotinib hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Mar 2008
- 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
DISEASE CHARACTERISTICS:
- Histologically confirmed glioblastoma multiforme (or high-grade glioma that is behaving clinically and/or radiographically like glioblastoma multiforme)
- Progressed after first-line therapy (e.g., surgery, chemotherapy, or radiotherapy)
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- ANC > 1,500/mm³
- Platelet count > 100,000/mm³
- Hemoglobin > 8.5 g/dL
- ALT and AST < 2 times upper limit of normal (ULN)
- Alkaline phosphatase < 2 times ULN
- Bilirubin < 1.5 mg/dL
- Creatinine < 1.5 mg/dL OR creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No diagnosis or history of significant renal or hepatic disease
- No contraindication (e.g., mass effect, brain shift) to lumbar puncture procedure
- No active infection
- No diagnosis or history of corneal abnormalities
- No diagnosis or history of malabsorptive syndrome or other disorder affecting gastrointestinal absorption
- No history of hypersensitivity reactions to midazolam hydrochloride (CYP3A4 biomarker)
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial locations and contacts
1 site in 1 country.
United States1 site
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, 27599-7295
About this study
Official title: Phase I Study of Erlotinib Administered Every 72 Hours in Patients With Glioblastoma Multiforme With Pharmacokinetic/Pharmacodynamic Correlates
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib in treating patients with progressive glioblastoma multiforme.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of erlotinib hydrochloride when administered in escalating doses every 72 hours in patients with progressive glioblastoma multiforme.
Secondary
- Determine the relationship between plasma and cerebrospinal fluid (CSF) concentrations of erlotinib hydrochloride in these patients.
- Determine the relationship between plasma and CSF concentrations of erlotinib hydrochloride in patients not receiving concurrent enzyme-inducing antiepileptic drugs (EIAEDs) vs those receiving concurrent EIAEDs.
- Correlate CYP3A4 activity, as measured by midazolam hydrochloride clearance, with plasma clearance of erlotinib hydrochloride in these patients.
- Correlate CYP1A2 activity, as measured by the 4-hour paraxanthine (17X)/caffeine (137X) plasma ratio, with plasma clearance of erlotinib hydrochloride in these patients.
- Determine, preliminarily, objective response and disease progression in patients treated with erlotinib hydrochloride.
- Correlate the presence of EGFRvIII mutation with objective response and disease progression in patients treated with erlotinib hydrochloride.
OUTLINE: This is an open-label, dose-escalation study. Patients are stratified according to use of concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no).
Patients receive oral erlotinib hydrochloride once every 72 hours for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses* of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined or preliminary results show no direct relationship between plasma and cerebrospinal fluid concentrations. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
NOTE: *Interim enrollment of patients is allowed; these patients receive the current approved dose of erlotinib hydrochloride.
Patients undergo blood sample collection periodically on day 13 for pharmacokinetic studies. The pharmacokinetic study comprises midazolam hydrochloride and caffeine clearance assessment and correlation of these assessments with CYP3A4 activity and CYP1A2 activity.
Paraffin-embedded and frozen tumor tissue is obtained from patients who underwent prior surgical resection for analysis of wild-type EGFR and EGFRvIII mutation by immunohistochemistry.
Quality of life is assessed at baseline and then at 1 month and 6 months.
After completion of study therapy, patients are followed periodically.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- erlotinib hydrochloride
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma, recurrent adult brain tumor
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
300 mg, per day for subjects taking EIAEDs
150 mg, per day for those NOT taking EIAEDs
| Study group | Role | What they receive |
|---|---|---|
| Subjects receiving EIAEDs | Experimental | Patients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED) Receives: Drug: erlotinib hydrochloride |
| Subjects NOT taking EIAEDs | Experimental | Patients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED) Receives: Drug: erlotinib hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival
Progression -free survival will be measured by radographic response using RECIST critera.
Measured: 12 months
Correlation between presence of the EGFRvIII mutation with treatment outcomes
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2005 (estimated)
- Study startSep 2005
- Primary completionFeb 2008
- Study completionMar 2008
Why it stopped: Loss of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Celeste Lindley, PharmD, Principal investigator, UNC Lineberger Comprehensive Cancer CenterFrances A. Collichio, MD, Principal investigator, UNC Lineberger Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00227032
- Sponsor's protocol ID
- LCCC 0424
- Other IDs
- CDR0000550155
- Status last verified
- Mar 2012
- First submitted
- 23 Sep 2005
- Last updated
- 6 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Erlotinib Administered Every 72 Hours in Patients With Glioblastoma Multiforme With Pharmacokinetic/Pharmacodynamic Correlates
- ClinicalTrials.gov ID
- NCT00227032
- Acronym / sponsor ID
- LCCC 0424
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult glioblastoma, recurrent adult brain tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Loss of funding
- Enrolment
- 10 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2005
- Primary completion
- Feb 2008 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 27 Sep 2005 (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.
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib in treating patients with progressive glioblastoma multiforme.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of erlotinib hydrochloride when administered in escalating doses every 72 hours in patients with progressive glioblastoma multiforme.
Secondary
- Determine the relationship between plasma and cerebrospinal fluid (CSF) concentrations of erlotinib hydrochloride in these patients.
- Determine the relationship between plasma and CSF concentrations of erlotinib hydrochloride in patients not receiving concurrent enzyme-inducing antiepileptic drugs (EIAEDs) vs those receiving concurrent EIAEDs.
- Correlate CYP3A4 activity, as measured by midazolam hydrochloride clearance, with plasma clearance of erlotinib hydrochloride in these patients.
- Correlate CYP1A2 activity, as measured by the 4-hour paraxanthine (17X)/caffeine (137X) plasma ratio, with plasma clearance of erlotinib hydrochloride in these patients.
- Determine, preliminarily, objective response and disease progression in patients treated with erlotinib hydrochloride.
- Correlate the presence of EGFRvIII mutation with objective response and disease progression in patients treated with erlotinib hydrochloride.
OUTLINE: This is an open-label, dose-escalation study. Patients are stratified according to use of concurrent enzyme-inducing antiepileptic drugs (EIAEDs) (yes vs no).
Patients receive oral erlotinib hydrochloride once every 72 hours for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses* of erlotinib hydrochloride until the maximum tolerated dose (MTD) is determined or preliminary results show no direct relationship between plasma and cerebrospinal fluid concentrations. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
NOTE: *Interim enrollment of patients is allowed; these patients receive the current approved dose of erlotinib hydrochloride.
Patients undergo blood sample collection periodically on day 13 for pharmacokinetic studies. The pharmacokinetic study comprises midazolam hydrochloride and caffeine clearance assessment and correlation of these assessments with CYP3A4 activity and CYP1A2 activity.
Paraffin-embedded and frozen tumor tissue is obtained from patients who underwent prior surgical resection for analysis of wild-type EGFR and EGFRvIII mutation by immunohistochemistry.
Quality of life is assessed at baseline and then at 1 month and 6 months.
After completion of study therapy, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects receiving EIAEDs | Experimental | Drug: erlotinib hydrochloridePatients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED) |
| Subjects NOT taking EIAEDs | Experimental | Drug: erlotinib hydrochloridePatients will be stratified according to concurrent use of enzyme inducing anti-epileptic drugs (EIAED) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| erlotinib hydrochloride300 mg, per day for subjects taking EIAEDs 150 mg, per day for those NOT taking EIAEDs | Drug | Subjects NOT taking EIAEDs, Subjects receiving EIAEDs |
Primary outcome
Progression-free survival
Time frame: 12 months
Progression -free survival will be measured by radographic response using RECIST critera.
Correlation between presence of the EGFRvIII mutation with treatment outcomes
Time frame: 6 months
Results and safety
The study was stopped early (reason given: Loss of funding). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2012.
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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.
Celeste Lindley, PharmD principal investigator
UNC Lineberger Comprehensive Cancer Center
Frances A. Collichio, MD principal investigator
UNC Lineberger Comprehensive Cancer Center
1 site 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 hydrochloride in people with Brain and Central Nervous System Tumors, run by UNC Lineberger Comprehensive Cancer Center 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?
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: stopped early, as of the sponsor's last update on 6 Mar 2012. 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 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 was stopped early (reason given: Loss of funding). Results are not available in the source record.
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?
Progression-free survival (time frame: 12 months). The study lists 2 primary outcomes in all. 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 6 Mar 2012.