Adult Anaplastic AstrocytomaPhase 1NCT00093613
Sorafenib in Treating Patients With Recurrent or Progressive Malignant Glioma
A Phase 1 study testing sorafenib tosylate and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 10 sites in United States.
Trial summary
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with recurrent or progressive malignant glioma. Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma
- What is being tested?
- 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
- 47 participants
- Where
- 10 sitesUnited States
- Study dates
- Dec 2004to Dec 2011
- 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
- Patients must have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or 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 measurable progressive or recurrent malignant glioma 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
- 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
- Platelets >= 100,000/mm^3
Show all 13Show fewer
- Creatinine =< 1.7mg/dl
- Total Bilirubin =< 1.5mg/dl
- Transaminases =< 4 times above the upper limits of the institutional norm
- PT, PTT, INR within 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 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 receiving concurrent therapy for their tumor (with the exception of steroids)
- 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
- Patients must not be on therapeutic anticoagulation; prophylactic anticoagulation (i.e. low dose warfarin) of venous or arterial access devices is allowed provided that the requirements for PT, INR or PTT are met; (Patients will be taken off treatment if they require therapeutic anticoagulation during BAY 43-9006 treatment)
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Emory University/Winship Cancer Institute
Atlanta, Georgia, 30322
Adult Brain Tumor Consortium
Baltimore, Maryland, 21231-1000
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase I Trial of BAY 43-9006 for Patients With Recurrent or Progressive Malignant Glioma
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with recurrent or progressive malignant glioma. Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of BAY 43-9006 when administered to adults with recurrent malignant glioma, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.
II. To assess and estimate the dose-related toxicities. III. To describe the pharmacokinetics of this route of administration, measuring BAY 43-9006, and to assess the pharmacokinetic difference between patients taking enzyme-inducing agents and those who are not.
IV. To estimate overall survival.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to the concurrent use of cytochrome P450-inducing anticonvulsants (yes vs no).
Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
Patients are followed every 2 months.
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Being tested
- sorafenib tosylate, pharmacological study
- Medical subject headings
- Astrocytoma, Oligodendroglioma, Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib tosylateDrug
Also called BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, Nexavar
Given PO
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (sorafenib tosylate) | Experimental | Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. Receives: Drug: sorafenib tosylate; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of sorafenib tosylate in patients with recurrent or progressive malignant glioma, receiving (group A) or not receiving (group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex
Measured: 28 days
Secondary outcomes (4)
Frequency of the toxicities associated with sorafenib tosylate treatment between patients with recurrent or progressive malignant glioma, receiving or not receiving anticonvulsants
The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.
Measured: Up to 6 years
Effect of taking enzyme inducing anticonvulsant drugs on the pharmacokinetics and metabolism of sorafenib tosylate
The geometric mean +/- standard deviation of the estimated values of the pharmacokinetic parameter for groups of patients evaluated at each dose level will be calculated. Parametric statistical tests (ie, single factor ANOVA, Student's t-test) of pharmacokinetic variables will be performed after logarithmic transformation of the data. All tests will be two-sided and a value of P < 0.05 will be used as the criteria for significance.
Measured: Days 1 and 15 of course 1 and day 15 of course 2
Magnitude of variability in the steady-state pharmacokinetics of the drug both within and between patients
The geometric mean +/- standard deviation of the estimated values of the pharmacokinetic parameter for groups of patients evaluated at each dose level will be calculated. Parametric statistical tests (ie, single factor ANOVA, Student's t-test) of pharmacokinetic variables will be performed after logarithmic transformation of the data. All tests will be two-sided and a value of P < 0.05 will be used as the criteria for significance.
Measured: Days 1 and 15 of course 1 and day 15 of course 2
Overall survival
Non-parametric estimates of survival will be calculated. An overall failure rate will be estimated along with the 95% confidence interval. The overall failure rate is expressed as hazard of failure per person-year of follow-up (the number of deaths divided by the total exposure time in the study cohort).
Measured: From the time of first day of treatment to death occurrence, assessed up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2004 (estimated)
- Study startDec 2004
- Primary completionOct 2010
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Anaplastic AstrocytomaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Louis Nabors, Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00093613
- Sponsor's protocol ID
- NCI-2012-03102
- Other IDs
- NCI-2012-03102, NABTT-0401, ABTC-0401, NABTT 0401, NABTT-0401, U01CA062475
- Status last verified
- Dec 2013
- First submitted
- 6 Oct 2004
- Last updated
- 30 May 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of BAY 43-9006 for Patients With Recurrent or Progressive Malignant Glioma
- ClinicalTrials.gov ID
- NCT00093613
- Acronym / sponsor ID
- NCI-2012-03102
- Conditions
- Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2004
- Primary completion
- Oct 2010 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 8 Oct 2004 (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.
This phase I trial is studying the side effects and best dose of sorafenib in treating patients with recurrent or progressive malignant glioma. Sorafenib may stop the growth of tumor cells by stopping blood flow to the tumor and by blocking the enzymes necessary for their growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the maximum tolerated dose (MTD) of BAY 43-9006 when administered to adults with recurrent malignant glioma, receiving (Group A) or not receiving (Group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex.
II. To assess and estimate the dose-related toxicities. III. To describe the pharmacokinetics of this route of administration, measuring BAY 43-9006, and to assess the pharmacokinetic difference between patients taking enzyme-inducing agents and those who are not.
IV. To estimate overall survival.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to the concurrent use of cytochrome P450-inducing anticonvulsants (yes vs no).
Patients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.
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 (sorafenib tosylate) | Experimental | Drug: sorafenib tosylate, Other: pharmacological studyPatients receive oral sorafenib twice daily on days 1-28 (once daily on day 1 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients per stratum receive escalating doses of sorafenib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must have histologically proven malignant glioma (anaplastic astrocytoma, anaplastic oligodendroglioma or 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 measurable progressive or recurrent malignant glioma 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
- 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
Key exclusion criteria (7 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 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 receiving concurrent therapy for their tumor (with the exception of steroids)
- 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
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 |
|---|---|---|
| sorafenib tosylateAlso: BAY 43-9006, BAY 43-9006 Tosylate Salt, BAY 54-9085, NexavarGiven PO | Drug | Treatment (sorafenib tosylate) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (sorafenib tosylate) |
Primary outcome
Maximum tolerated dose (MTD) of sorafenib tosylate in patients with recurrent or progressive malignant glioma, receiving (group A) or not receiving (group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex
Time frame: 28 days
4 secondary outcomes
Frequency of the toxicities associated with sorafenib tosylate treatment between patients with recurrent or progressive malignant glioma, receiving or not receiving anticonvulsants
Time frame: Up to 6 years
Effect of taking enzyme inducing anticonvulsant drugs on the pharmacokinetics and metabolism of sorafenib tosylate
Time frame: Days 1 and 15 of course 1 and day 15 of course 2
Magnitude of variability in the steady-state pharmacokinetics of the drug both within and between patients
Time frame: Days 1 and 15 of course 1 and day 15 of course 2
Overall survival
Time frame: From the time of first day of treatment to death occurrence, assessed up to 6 years
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 30 May 2014.
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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.
Louis Nabors principal investigator
National Cancer Institute (NCI)
10 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 sorafenib tosylate and pharmacological study in people with Adult Anaplastic Astrocytoma and Adult Anaplastic Oligodendroglioma, run by National Cancer Institute (NCI) at 10 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 13 inclusion and 7 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 30 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 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?
Maximum tolerated dose (MTD) of sorafenib tosylate in patients with recurrent or progressive malignant glioma, receiving (group A) or not receiving (group B) anticonvulsants known to be metabolized by the P450 hepatic enzyme complex (time frame: 28 days). 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 30 May 2014; AzTrials last refreshed its copy on 8 Nov 2026.