Brain and Central Nervous System TumorsPhase 1NCT00509431
Erlotinib and Sirolimus in Treating Patients With Recurrent Malignant Glioma
A Phase 1 study testing Erlotinib + Sirolimus in people with Brain and Central Nervous System Tumors, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent… 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 + Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2006to Sep 2012
- 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 malignant glioma, including any of the following:
- Glioblastoma multiforme (GBM)
- Gliosarcoma (GS)
- Anaplastic astrocytoma (AA)
- Anaplastic oligodendroglioma (AO)
- Anaplastic mixed oligoastrocytomas (AMA)
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- Malignant astrocytoma not otherwise specified (NOS)
- Prior low-grade glioma allowed provided there is histologic evidence of progression to a malignant glioma
- Must meet the following criteria for phase I:
- All types of malignant gliomas allowed
- No limitations on the number of relapses
- Must meet the following criteria for phase II:
- Only patients with GBM or GS are allowed
- Must be in first, second, or third relapse
- patients who had prior therapy (must include external beam radiotherapy) for a low-grade glioma that is considered standard, non-surgical treatment for a high-grade glioma, the surgical diagnosis of high-grade glioma will be considered the first relapse
- Must have shown unequivocal radiographic evidence for tumor progression by MRI or CT scan and have either measurable or evaluable disease
- Measurable disease is defined as bidimensionally measurable lesions with clearly defined margins by MRI scan
- Evaluable disease is defined as unidimensionally measurable lesions or masses with margins not clearly defined
- Karnofsky performance status ≥ 60%
- Life expectancy > 8 weeks
- Absolute neutrophil count ≥ 1,500/μL
- Platelets ≥ 100,000/μL
- Total bilirubin < 2.0 x upper limit of institutional normal (ULN)
- AST < 2.0 x ULN
- Creatinine < 1.5 x ULN
- Fasting serum triglycerides < 2.5 x ULN
- Fasting serum cholesterol < 350 mg/dL
- Women of child-bearing potential and men must agree to use adequate contraception (i.e., hormonal or barrier method of birth control) prior to study entry and for the duration of study participation
- Recovered from all toxicities associated with prior surgery, radiotherapy, or chemotherapy
- At least 1 week since prior surgery
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas)
- At least 12 weeks since prior radiation therapy
- Must not receive any P450-enzyme-inducing anticonvulsants (EIAC) for at least 2 weeks prior to and during participation in this trial
Who cannot join
- Women who are pregnant or lactating
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or sirolimus
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection requiring IV antibiotics
- Symptomatic congestive heart failure
- Unstable angina pectoris
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- Cardiac arrhythmia
- Hyperlipidemia (e.g., grade 3 or greater hypercholesterolemia or hypertriglyceridemia) not controlled with medication
- Psychiatric illness or social situations that would limit compliance with study requirements
- Disorders associated with significant immunocompromise (e.g., HIV or systemic lupus erythematosus [SLE])
- Patients with another primary malignancy that has required treatment other than surgery within the past year (except for nonmelanoma skin cancer or carcinoma in situ)
- Patients with the inability to comply with the protocol requirements in the opinion of the investigator including those who can not take oral medications
- Patients who are unable to undergo routine imaging evaluations with magnetic resonance imaging scans
- Prior EGFR-directed or mTOR-directed therapies including sirolimus or sirolimus analogs
- Patients taking concurrent immunosuppressive agents other than prescribed corticosteroids
- Concurrent antineoplastic or antitumor agents that are not part of the study therapy including chemotherapy, radiation therapy, immunotherapy, and hormonal anticancer therapy
- Blood products during cycle 1 unless a patient experiences hematologic DLT or if it is medically imperative to administer a transfusion
- Concurrent grapefruit or grapefruit juice
- Other concurrent investigational agents
- Receiving concurrent enzyme-inducing antiepileptic drugs
Trial locations and contacts
1 site in 1 country.
United States1 site
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095-1781
About this study
Official title: A Phase I/II, Dual-Center, Open-Label Trial of the Safety and Efficacy of Tarceva™ (Erlotinib Hydrochloride) Plus Sirolimus in Patients With Recurrent Malignant Glioma Not on P450-Inducing Anti-Epileptics
RATIONALE: Erlotinib and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of erlotinib hydrochloride in combination with sirolimus in adult patients with malignant glioma, who are not receiving enzyme-inducing anti-epileptic drugs (EIAED). (Phase I)
- Evaluate preliminary efficacy (response rate [RR], progression-free survival [PFS], and overall survival [OS]) of erlotinib hydrochloride and sirolimus combination therapy in glioblastoma multiforme (GMB)/gliosarcoma (GS) patients who are not undergoing surgery at the time of recurrence or relapse (dose-expansion arm). (Phase II)
- Evaluate molecular determinants of response to the combination of erlotinib hydrochloride and sirolimus, especially the roles of the mutation of EGFR (e.g., vIII mutant, other somatic mutations of vIII, and mutation/deletion of PTEN).
Secondary
- To characterize the safety and tolerability of erlotinib hydrochloride and sirolimus combination therapy in these patient populations.
- To characterize the single-dose and repeated-dose pharmacokinetic (PK) profiles of erlotinib hydrochloride (in serum) and sirolimus (in whole blood) combination therapy in these patient populations.
- To characterize, in pre- and/or post-treatment tumor samples, when available, expression levels of total and activated phosphorylated proteins relevant to the EGFR, VEGFR, and PI3K/mTOR signaling pathways, relevant downstream signaling network components, EGFR and VEGFR-related ligands, apoptosis (TUNEL), cell cycle control, and proliferation.
- To assess pre- and/or post-treatment tumor samples, when available, for DNA-based changes (e.g., EGFR [DNA] amplification, EGFR and EGFRvIII mutations, and mutations/deletions in the PTEN gene) relevant to the molecular biology in GBM.
OUTLINE: Patients receive oral erlotinib hydrochloride and sirolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor tissue and blood sample collection periodically for pharmacological and biological studies. Samples are analyzed for concentrations of erlotinib hydrochloride and trough serum levels of sirolimus via HPLC, EGFR, EGFRvIII, PTEN and the phospho-specific antibodies associated with the MAPK and PI3K pathways via IHC, and EGFRvIII and sequencing of EGFR, PTEN and other critical genes via PCR, gene expression, and SNP analysis. Germline DNA will also be used to distinguish polymorphisms from somatic mutations in gene sequenced.
After completion of study treatment, patients are followed periodically.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- Erlotinib + Sirolimus
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor, adult glioblastoma, adult pilocytic astrocytoma, adult diffuse astrocytoma, adult subependymal giant cell astrocytoma, adult oligodendroglioma
- Medical subject headings
- Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma, Astrocytoma, Oligodendroglioma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Erlotinib + SirolimusDrug
In arm I of dose escalation phase,starting dose of erlotinib is 150 mg daily. Starting dose of sirolimus includes a 15 mg loading dose, followed by continuous dosing at 5 mg daily.Dose escalation will proceed according to protocol Phase II of the study was not conducted only Phase I
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + Sirolimus | Experimental | This is an open-label,phase I single-arm dose-escalation and phase II study of continuous, once daily doses of erlotinib administered orally in combination with sirolimus in adult patients with malignant glioma at first, second or third recurrence Receives: Drug: Erlotinib + Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine maximum tolerated dose and dose limiting toxicity of escalating doses of erlotinib in combination with sirolimus
Measured: day 28 of cycle 1
Secondary outcomes (2)
To characterize the single-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations
Measured: Day 1 of cycle 1
To characterize repeated-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations
Measured: Day 28 of cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2007 (estimated)
- Study startAug 2006
- Primary completionDec 2011
- Study completionSep 2012
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 Jonsson 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy F. Cloughesy, MD, Principal investigator, Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00509431
- Sponsor's protocol ID
- CDR0000557423
- Other IDs
- UCLA-0604104
- Status last verified
- Feb 2016
- First submitted
- 30 Jul 2007
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II, Dual-Center, Open-Label Trial of the Safety and Efficacy of Tarceva™ (Erlotinib Hydrochloride) Plus Sirolimus in Patients With Recurrent Malignant Glioma Not on P450-Inducing Anti-Epileptics
- ClinicalTrials.gov ID
- NCT00509431
- Acronym / sponsor ID
- CDR0000557423
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor, adult glioblastoma, adult pilocytic astrocytoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- Aug 2006
- Primary completion
- Dec 2011 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 31 Jul 2007 (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 and sirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with sirolimus and to see how well they work in treating patients with recurrent malignant glioma.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of erlotinib hydrochloride in combination with sirolimus in adult patients with malignant glioma, who are not receiving enzyme-inducing anti-epileptic drugs (EIAED). (Phase I)
- Evaluate preliminary efficacy (response rate [RR], progression-free survival [PFS], and overall survival [OS]) of erlotinib hydrochloride and sirolimus combination therapy in glioblastoma multiforme (GMB)/gliosarcoma (GS) patients who are not undergoing surgery at the time of recurrence or relapse (dose-expansion arm). (Phase II)
- Evaluate molecular determinants of response to the combination of erlotinib hydrochloride and sirolimus, especially the roles of the mutation of EGFR (e.g., vIII mutant, other somatic mutations of vIII, and mutation/deletion of PTEN).
Secondary
- To characterize the safety and tolerability of erlotinib hydrochloride and sirolimus combination therapy in these patient populations.
- To characterize the single-dose and repeated-dose pharmacokinetic (PK) profiles of erlotinib hydrochloride (in serum) and sirolimus (in whole blood) combination therapy in these patient populations.
- To characterize, in pre- and/or post-treatment tumor samples, when available, expression levels of total and activated phosphorylated proteins relevant to the EGFR, VEGFR, and PI3K/mTOR signaling pathways, relevant downstream signaling network components, EGFR and VEGFR-related ligands, apoptosis (TUNEL), cell cycle control, and proliferation.
- To assess pre- and/or post-treatment tumor samples, when available, for DNA-based changes (e.g., EGFR [DNA] amplification, EGFR and EGFRvIII mutations, and mutations/deletions in the PTEN gene) relevant to the molecular biology in GBM.
OUTLINE: Patients receive oral erlotinib hydrochloride and sirolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo tumor tissue and blood sample collection periodically for pharmacological and biological studies. Samples are analyzed for concentrations of erlotinib hydrochloride and trough serum levels of sirolimus via HPLC, EGFR, EGFRvIII, PTEN and the phospho-specific antibodies associated with the MAPK and PI3K pathways via IHC, and EGFRvIII and sequencing of EGFR, PTEN and other critical genes via PCR, gene expression, and SNP analysis. Germline DNA will also be used to distinguish polymorphisms from somatic mutations in gene sequenced.
After completion of study treatment, patients are followed periodically.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + Sirolimus | Experimental | Drug: Erlotinib + SirolimusThis is an open-label,phase I single-arm dose-escalation and phase II study of continuous, once daily doses of erlotinib administered orally in combination with sirolimus in adult patients with malignant glioma at first, second or third recurrence |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (33 listed)
- Histologically confirmed malignant glioma, including any of the following:
- Glioblastoma multiforme (GBM)
- Gliosarcoma (GS)
- Anaplastic astrocytoma (AA)
- Anaplastic oligodendroglioma (AO)
Key exclusion criteria (20 listed)
- Women who are pregnant or lactating
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to erlotinib hydrochloride or sirolimus
- Uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection requiring IV antibiotics
- Symptomatic congestive heart failure
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 + SirolimusIn arm I of dose escalation phase,starting dose of erlotinib is 150 mg daily. Starting dose of sirolimus includes a 15 mg loading dose, followed by continuous dosing at 5 mg daily.Dose escalation will proceed according to protocol Phase II of the study was not conducted only Phase I | Drug | Erlotinib + Sirolimus |
Primary outcome
To determine maximum tolerated dose and dose limiting toxicity of escalating doses of erlotinib in combination with sirolimus
Time frame: day 28 of cycle 1
2 secondary outcomes
To characterize the single-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations
Time frame: Day 1 of cycle 1
To characterize repeated-dose pharmacokinetic (PK) profile of erlotinib (in serum) and sirolimus (in whole blood) combination therapy in these patient populations
Time frame: Day 28 of cycle 1
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 31 Jul 2020.
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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.
Timothy F. Cloughesy, MD principal investigator
Jonsson 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 + Sirolimus in people with Brain and Central Nervous System Tumors, run by Jonsson 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?
The sponsor lists 33 inclusion and 20 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 31 Jul 2020. 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 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?
To determine maximum tolerated dose and dose limiting toxicity of escalating doses of erlotinib in combination with sirolimus (time frame: day 28 of cycle 1). 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 31 Jul 2020.