Adult Giant Cell GlioblastomaPhase 2NCT00445588
Erlotinib and Sorafenib in Treating Patients With Progressive or Recurrent Glioblastoma Multiforme
A Phase 2 study testing erlotinib hydrochloride, sorafenib tosylate and pharmacological study in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 9 sites in United States.
Trial summary
This phase II trial is studying how well giving erlotinib together with sorafenib works in treating patients with progressive or recurrent glioblastoma multiforme. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma
- What is being tested?
- erlotinib hydrochloride, sorafenib tosylate and pharmacological study
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 9 sitesUnited States
- Study dates
- Jan 2007to Aug 2009
- Phase
- Phase 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed supratentorial glioblastoma multiforme which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previous low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have a high grade glioma are eligible
- Patients must have tissue specimens available and agree to have their blood and tissue blocks (or slides) submitted for the combined correlative studies
- Patients must have measurable contrast enhancing progressive or recurrent glioblastoma multiforme by MRI or CT imaging (Within 14 days before starting treatment)
- Patients must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen; NOTE: For a non-cytotoxic, FDA approved agents (i.e. Celebrex, thalidomide, etc.) therapy could be started 2 weeks after discontinuing this agent provided the patient has fully recovered from all toxicity associated with the agent; for investigational, non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be eligible for this study
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
- Absolute Neutrophil Count >= 1500/mm^3
Show all 14Show fewer
- Platelets >= 100,000/mm^3
- Creatinine =< 1.7mg/dl
- Total Bilirubin within normal institutional limits
- Transaminases =< 2.5 times above the upper limits of the institutional norm
- PT, PTT ≤ institutional norm
- Patients must be able to provide written informed consent
- Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception; women of childbearing potential must have a negative serum pregnancy test; (the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant)
- Patients must have a Mini Mental State Exam score >= 15
Who cannot join
- Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
- Patients with uncontrolled hypertension; hypertension with systolic blood pressure of > 140 mmHg or diastolic pressure > 90 mmHg; however, patients with well-controlled hypertension are eligible
- Patients who are pregnant or breast-feeding (the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant)
- Patients who have received more than two prior treatments
- Patients who have had prior therapy with erlotinib or sorafenib or any other agent targeting EGFR
- Patients receiving concurrent therapy for their tumor (with the exception of steroids)
Show all 21Show fewer
- Patients undergoing major surgery or sustaining a significant traumatic injury within 21 days prior to treatment are ineligible
- Patients with a concurrent malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin; patients with a prior malignancy are ineligible unless they have been free of disease for >= five years
- Patients must not have any evidence of bleeding diathesis or coagulopathy
- Patients with PT INR > 1.5 are excluded, unless the patient is on full dose warfarin
- Patients on full-dose anticoagulants (e.g., warfarin) are eligible provided that both of the following criteria are met:
- The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
- The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
- NOTE: Patients on a full dose of anticoagulants will a different schedule for PT/INR evaluations
- Prophylactic anticoagulation (i.e. low dose warfarin) are eligible provided their coagulation parameter levels are as follows: prothrombin time (INR; International Normalized Ratio of prothrombin time) < 1.1 x institutional upper limit of normal
- Patients with known abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjogren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test) are excluded
- Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow pills are excluded
- Patients cannot be receiving cytochrome P450-inducing anticonvulsants (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital, primidone, oxcarbazepine) and must not have taken them for at least 10 days
- Patients may not have allergies to or a history of allergic reactions attributed to erlotinib and/or sorafenib
- Eligibility of patients receiving any other medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of erlotinib or sorafenib will be determined following review of their case by the Principal Investigator
- HIV patients receiving combination anti-retroviral therapy will be excluded
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Emory University
Atlanta, Georgia, 30322
Johns Hopkins University
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital
Boston, Massachusetts, 02114
Cleveland Clinic
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Moffitt Cancer Center
Tampa, Florida, 33612
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase II Trial of Erlotinib (OSI-774) and Sorafenib (BAY 43-9006) for Patients With Progression or Recurrent Glioblastoma Multiforme
This phase II trial is studying how well giving erlotinib together with sorafenib works in treating patients with progressive or recurrent glioblastoma multiforme. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving erlotinib together with sorafenib may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- The primary objective of this trial is to estimate the overall survival rate associated with this combined regimen in treating adult patients with recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
- To assess and estimate the toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To describe the pharmacokinetics of this route of administration. V. For the Molecular Targeted Combinations Correlative (MTC2) Study Initiative: To determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents.
OUTLINE: This is a multicenter, open-label, phase II study.
Patients receive oral erlotinib hydrochloride once daily and oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Tumor tissue and blood samples are collected prior to beginning treatment. Samples are analyzed by immunohistochemistry, gene expression, and DNA mutation and genomic analyses of the epidermal growth factor receptor, ras-raf-ERK, and PI3K-Akt-mTOR pathways to identify markers that correlate with patient outcomes. Blood samples are also collected on day 15 of course 1 for pharmacokinetic studies. Samples are analyzed by reversed-phase isocratic high-performance liquid chromatography with electrospray ionization mass spectrometry to determine the concentration of erlotinib hydrochloride and sorafenib tosylate and its known metabolites.
After completion of study therapy, patients are followed every 2 months.
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- erlotinib hydrochloride, sorafenib tosylate, pharmacological study
- Medical subject headings
- 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
Also called OSI-774
150mg Given orally once daily
sorafenib tosylateDrug
Also called BAY 3-9006
400mg Given orally twice daily
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients receive oral erlotinib hydrochloride 150mg once daily and oral sorafenib tosylate 400mg twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Other: pharmacological study Receives: Drug: erlotinib hydrochloride; Drug: sorafenib tosylate; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
death. measured by time of first day of treatment until date of death, assessed up to 2 years.
Measured: Time of first day of the treatment to death, assessed up to 2 years
Secondary outcomes (1)
6months -Progression-free Survival Rate
defined patient started treatment is alive and progression free at the time of 26-week (6 months) follow-up
Measured: At 6 months- defined as patient started treatment is alive and progression free at the time of 26-week (6 months) follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2007 (estimated)
- Study startJan 2007
- Primary completionAug 2009
- Study completionAug 2009
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 Adult Giant Cell GlioblastomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- David Peereboom, MD, Principal investigator, New Approaches to Brain Tumor Therapy Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00445588
- Sponsor's protocol ID
- NCI-2012-03018
- Other IDs
- NCI-2012-03018, CDR531731, NABTT 0502, NABTT-0502, U01CA062475
- Status last verified
- Mar 2016
- First submitted
- 7 Mar 2007
- Last updated
- 27 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Peereboom DM, Ahluwalia MS, Ye X, Supko JG, Hilderbrand SL, Phuphanich S, Nabors LB, Rosenfeld MR, Mikkelsen T, Grossman SA; New Approaches to Brain Tumor Therapy Consortium. NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme. Neuro Oncol. 2013 Apr;15(4):490-6. doi: 10.1093/neuonc/nos322. Epub 2013 Jan 17.
PubMed 23328813
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Erlotinib (OSI-774) and Sorafenib (BAY 43-9006) for Patients With Progression or Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00445588
- Acronym / sponsor ID
- NCI-2012-03018
- Conditions
- Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2007
- Primary completion
- Aug 2009 (actual)
- Study completion
- Aug 2009 (actual)
- First posted
- 9 Mar 2007 (estimated)
- Results
- Posted 27 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well giving erlotinib together with sorafenib works in treating patients with progressive or recurrent glioblastoma multiforme. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving erlotinib together with sorafenib may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- The primary objective of this trial is to estimate the overall survival rate associated with this combined regimen in treating adult patients with recurrent glioblastoma multiforme.
SECONDARY OBJECTIVES:
- To assess and estimate the toxicities. II. Tumor response rate. III. To estimate 6-month progression free survival. IV. To describe the pharmacokinetics of this route of administration. V. For the Molecular Targeted Combinations Correlative (MTC2) Study Initiative: To determine the relationship between tumor and blood biomarkers and clinical outcome of patients treated with the combination of targeted agents.
OUTLINE: This is a multicenter, open-label, phase II study.
Patients receive oral erlotinib hydrochloride once daily and oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
Tumor tissue and blood samples are collected prior to beginning treatment. Samples are analyzed by immunohistochemistry, gene expression, and DNA mutation and genomic analyses of the epidermal growth factor receptor, ras-raf-ERK, and PI3K-Akt-mTOR pathways to identify markers that correlate with patient outcomes. Blood samples are also collected on day 15 of course 1 for pharmacokinetic studies. Samples are analyzed by reversed-phase isocratic high-performance liquid chromatography with electrospray ionization mass spectrometry to determine the concentration of erlotinib hydrochloride and sorafenib tosylate and its known metabolites.
After completion of study therapy, patients are followed every 2 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: erlotinib hydrochloride, Drug: sorafenib tosylate, Other: pharmacological studyPatients receive oral erlotinib hydrochloride 150mg once daily and oral sorafenib tosylate 400mg twice daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Other: pharmacological study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have histologically confirmed supratentorial glioblastoma multiforme which is progressive or recurrent after radiation therapy ± chemotherapy; patients with previous low grade glioma who progressed after radiotherapy ± chemotherapy and are biopsied and found to have a high grade glioma are eligible
- Patients must have tissue specimens available and agree to have their blood and tissue blocks (or slides) submitted for the combined correlative studies
- Patients must have measurable contrast enhancing progressive or recurrent glioblastoma multiforme by MRI or CT imaging (Within 14 days before starting treatment)
- Patients must have recovered from toxicity of prior therapy. An interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy, while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen, and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen; NOTE: For a non-cytotoxic, FDA approved agents (i.e. Celebrex, thalidomide, etc.) therapy could be started 2 weeks after discontinuing this agent provided the patient has fully recovered from all toxicity associated with the agent; for investigational, non-cytotoxic agents a minimum of 3 weeks must have elapsed before the patient will be eligible for this study
- Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
Key exclusion criteria (21 listed)
- Patients with serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety; (examples of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements)
- Patients with uncontrolled hypertension; hypertension with systolic blood pressure of > 140 mmHg or diastolic pressure > 90 mmHg; however, patients with well-controlled hypertension are eligible
- Patients who are pregnant or breast-feeding (the anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant)
- Patients who have received more than two prior treatments
- Patients who have had prior therapy with erlotinib or sorafenib or any other agent targeting EGFR
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 hydrochlorideAlso: OSI-774150mg Given orally once daily | Drug | Treatment |
| sorafenib tosylateAlso: BAY 3-9006400mg Given orally twice daily | Drug | Treatment |
| pharmacological studyCorrelative studies | Other | Treatment |
Primary outcome
Overall Survival
Time frame: Time of first day of the treatment to death, assessed up to 2 years
death. measured by time of first day of treatment until date of death, assessed up to 2 years.
1 secondary outcome
6months -Progression-free Survival Rate
Time frame: At 6 months- defined as patient started treatment is alive and progression free at the time of 26-week (6 months) follow-up
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23328813Peereboom DM, Ahluwalia MS, Ye X, Supko JG, Hilderbrand SL, Phuphanich S, Nabors LB, Rosenfeld MR, Mikkelsen T, Grossman SA; New Approaches to Brain Tumor Therapy Consortium. NABTT 0502: a phase II and pharmacokinetic study of erlotinib and sorafenib for patients with progressive or recurrent glioblastoma multiforme. Neuro Oncol. 2013 Apr;15(4):490-6. doi: 10.1093/neuonc/nos322. Epub 2013 Jan 17.
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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.
David Peereboom, MD principal investigator
New Approaches to Brain Tumor Therapy Consortium
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing erlotinib hydrochloride, sorafenib tosylate and pharmacological study in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 9 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 14 inclusion and 21 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 27 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 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 27 Apr 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?
Overall Survival (time frame: Time of first day of the treatment to death, assessed up to 2 years). 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 NCT00445588, 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 27 Apr 2016.