Recurrent Glioblastoma MultiformePhase 2NCT00597493
Ph. 2 Sorafenib + Protracted Temozolomide in Recurrent GBM
A Phase 2 study testing Sorafenib and Temozolomide in people with Recurrent Glioblastoma Multiforme, run by Duke University at 1 site in United States.
Trial summary
PURPOSE AND OBJECTIVES: Primary Objective To evaluate the activity of Sorafenib plus protracted, daily temozolomide in patients with recurrent glioblastoma multiforme (GBM) as measured by 6-month PFS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Glioblastoma Multiforme
- What is being tested?
- Sorafenib and Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Dec 2010
- 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 diagnosis of recurrent/progressive GBM. Recurrence will be distinguished from "pseudoprogression" following XRT/Temodar as outlined in inclusion criteria 4.6 (below). Pts with recurrent disease whose diagnostic pathology confirmed glioblastoma multiforme will not need re-biopsy. Pts with prior low-grade glioma or WHO grade III malignant glioma are eligible if histologic assessment demonstrates transformation to GBM.
- Age > 18 years.
- Pts must be presenting in 1st, 2nd or 3rd relapse. Prior therapy must have included external beam radiotherapy.
- Adequate bone marrow, liver and renal function as assessed by following:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil ct (ANC) > 1,500/mm3
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- Platelet ct > 100,000/mm3
- Total bilirubin < 1.5 x ULN
- ALT \& AST < 2.5 x ULN ( < 5 x ULN for pts with liver involvement)
- INR < 1.5 or PT/PTT within normal limits (unless on therapeutic anti-coagulation). Pts receiving anti-coagulation treatment with agent such as warfarin or heparin may be allowed to participate. For pts on warfarin, INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by local standard of care, until INR is stable.
- Creatinine < 1.5 x ULN
- An interval of at least 2 weeks between prior surgical resection (1 week for biopsy)\& initiation of study regimen;
- An interval of at least 12 weeks from completion of standard, daily XRT, unless 1 of the following occurs: 1) new area of enhancement on MRI imaging that is outside XRT field; 2) biopsy proven recurrent tumor; 3) radiographic evidence of progressive tumor on 2 consecutive scans at least 4 weeks apart.
- An interval of at least 4 weeks from prior chemotherapy (except nitrosoureas which require 6 weeks) unless there is unequivocal evidence of tumor progression and pts has recovered from all anticipated toxicities from prior therapy.
- Karnofsky performance score > 60%.
- Ability to understand and willingness to sign written informed consent. A signed informed consent must be obtained prior to any study specific procedures.
- If sexually active, patients will take contraceptive measures (barrier method of birth control) for duration of treatments and for 3 months following discontinuation of sorafenib \& temozolomide.
- Pts who have had prior bevacizumab are eligible however interval of at least 6 weeks must have elapsed since their last dose.
Who cannot join
- Prior treatment with sorafenib.
- Significant cardiac disease including any of following: a) congestive heart failure > class II NYHA; b) unstable angina (anginal symptoms at rest); c) new onset angina (within last 3 months); d) myocardial infarction within past 6 months; e) cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Known severe hypersensitivity to sorafenib or any of excipients or temozolomide.
- Excessive risk of bleeding as defined by stroke within prior 6 months, history of CNS or intraocular bleed, or septic endocarditis.
- Female pts who are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control.
- Concurrent severe and/or uncontrolled medical disease that could compromise participation in study such as uncontrolled diabetes, uncontrolled hypertension, active clinically serious infection > CTCAE Grade 2, history of bleeding diathesis or coagulopathy, impairment of GI function or GI disease that may significantly alter absorption of the study regimen (i.e. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow tablets).
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- Thrombolic or embolic events such as cerebrovascular accident including transient ischemic attacks within past 6 months
- Pulmonary hemorrhage/bleeding event > CTCAE Grade 2 within 4 weeks of 1st dose of study drug.
- Any other hemorrhage/bleeding event > CTCAE Grade 3 within 4 weeks of 1st dose of study drug.
- Serious non-healing wound, ulcer, or bone fracture.
- Major surgery, open biopsy or significant traumatic injury within 4 weeks of 1st study drug.
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
- Pt is < 3 years free of another primary malignancy except: if other primary malignancy is not currently clinically significant or requiring active intervention, or if other primary malignancy is basal cell skin cancer or cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Pts unwilling or unable to comply with protocol including ability to swallow whole pills or presence of any malabsorption syndrome.
- Concurrent administration of St. John's Wort.
- Clinically serious infection requiring active intervention (CTCAE grade 2 or greater).
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase 2 Study of Sorafenib Plus Protracted Temozolomide in Recurrent Glioblastoma Multiforme
PURPOSE AND OBJECTIVES:
Primary Objective To evaluate the activity of Sorafenib plus protracted, daily temozolomide in patients with recurrent glioblastoma multiforme (GBM) as measured by 6-month PFS.
Secondary Objectives To evaluate the safety and toxicity of combination therapy using Sorafenib plus temozolomide; To determine the pharmacokinetics of Sorafenib when combined with temozolomide in patients on and not on concurrent EIAC medications.
Read the detailed description
STUDY ACTIVITIES AND POPULATION GROUP:
This is an open-label, non-randomized, single center phase 2 trial. A treatment cycle will consist of 4 weeks of therapy.
Sorafenib will be administered at a set dose of 400 mg (2 x 200 mg tablets) twice daily, without food (at least 1 hour before or 2 hours after eating). Temozolomide will be administered at a set dose of 50 mg/m2 once daily without food (at least 1 hour before or 2 hours after eating).
Thirty-two (32) patients will be enrolled in this single-stage study.
DATA ANALYSIS AND RISK/SAFETY ISSUES:
After 16 patients with recurrent GBM are treated, an interim analysis will be conducted. If 6 or more patients have experienced unacceptable toxicity, accrual of patients in this patient group will be terminated. Otherwise, patient accrual will continue. If 9 or more of the total 32 patients experience unacceptable toxicity, the treatment regimen will be considered to have an unacceptable toxicity profile. The type I and II error rates associated with this testing are 0.053 and 0.053, respectively.
- Conditions
- Recurrent Glioblastoma Multiforme
- Being tested
- Sorafenib and Temozolomide
- Keywords
- Recurrent Glioblastoma Multiforme, GBM, Glioblastoma, Sorafenib, Temozolomide, Brain Tumor, Recurrent GBM, Temodar, Gliosarcoma, Glioma, Nexavar
- Medical subject headings
- Glioblastoma, Brain Neoplasms, Gliosarcoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib and TemozolomideDrug
Also called Temodar, Nexavar
Temozolomide (50 mg per meter-squared of body surface area)every day by mouth in combination with sorafenib. Sorafenib will be taken by mouth twice every day. The dose of sorafenib will be 400 mg (2 x 200mg tablets).
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib + Temozolomide | Experimental | Subjects receive 400mg of Sorafenib twice daily and 50mg/m^2 of Temozolomide once daily
Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changes in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure Receives: Drug: Sorafenib and Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
6 Month Progression Free Survival (PFS)
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
Measured: 6 months
Secondary outcomes (4)
Safety and Toxicity of Combination
Number of participants experiencing a toxicity of at least grade 3 that was deemed possibly, probably, or definitely related to the treatment.
Measured: 16 months
Pharmacokinetics: C-max
Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. C-max refers to maximum plasma concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.
Measured: 13 months
Pharmacokinetics: T-max
Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. T-max refers to time to maximum concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.
Measured: 13 months
Pharmacokinetics: AUC-24
Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. AUC-24 refers to area under the plasma concentration-time curve from 0 to 24 hours. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAEDs) and those who were not were analyzed separately.
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2008 (estimated)
- Study startSep 2007
- Primary completionFeb 2009
- Study completionDec 2010
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 Recurrent Glioblastoma MultiformeStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer, Schering-Plough
- Responsible party
- Sponsor
- Investigators
- David A Reardon, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00597493
- Sponsor's protocol ID
- Pro00000464
- Status last verified
- May 2013
- First submitted
- 9 Jan 2008
- Last updated
- 24 Jun 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, Marcello J, Herndon JE 2nd, McLendon RE, Janney D, Friedman AH, Bigner DD, Friedman HS. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011 Jan;101(1):57-66. doi: 10.1007/s11060-010-0217-6. Epub 2010 May 5.
PubMed 20443129
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Study of Sorafenib Plus Protracted Temozolomide in Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00597493
- Acronym / sponsor ID
- Pro00000464
- Conditions
- Recurrent Glioblastoma Multiforme
- Keywords
- Recurrent Glioblastoma Multiforme, GBM, Glioblastoma, Sorafenib, Temozolomide, Brain Tumor, Recurrent GBM, Temodar
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Bayer, Schering-Plough
- Study start
- Sep 2007
- Primary completion
- Feb 2009 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 18 Jan 2008 (estimated)
- Results
- Posted 24 Jun 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PURPOSE AND OBJECTIVES:
Primary Objective To evaluate the activity of Sorafenib plus protracted, daily temozolomide in patients with recurrent glioblastoma multiforme (GBM) as measured by 6-month PFS.
Secondary Objectives To evaluate the safety and toxicity of combination therapy using Sorafenib plus temozolomide; To determine the pharmacokinetics of Sorafenib when combined with temozolomide in patients on and not on concurrent EIAC medications.
Detailed description
STUDY ACTIVITIES AND POPULATION GROUP:
This is an open-label, non-randomized, single center phase 2 trial. A treatment cycle will consist of 4 weeks of therapy.
Sorafenib will be administered at a set dose of 400 mg (2 x 200 mg tablets) twice daily, without food (at least 1 hour before or 2 hours after eating). Temozolomide will be administered at a set dose of 50 mg/m2 once daily without food (at least 1 hour before or 2 hours after eating).
Thirty-two (32) patients will be enrolled in this single-stage study.
DATA ANALYSIS AND RISK/SAFETY ISSUES:
After 16 patients with recurrent GBM are treated, an interim analysis will be conducted. If 6 or more patients have experienced unacceptable toxicity, accrual of patients in this patient group will be terminated. Otherwise, patient accrual will continue. If 9 or more of the total 32 patients experience unacceptable toxicity, the treatment regimen will be considered to have an unacceptable toxicity profile. The type I and II error rates associated with this testing are 0.053 and 0.053, respectively.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib + Temozolomide | Experimental | Drug: Sorafenib and TemozolomideSubjects receive 400mg of Sorafenib twice daily and 50mg/m^2 of Temozolomide once daily Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changes in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically confirmed diagnosis of recurrent/progressive GBM. Recurrence will be distinguished from "pseudoprogression" following XRT/Temodar as outlined in inclusion criteria 4.6 (below). Pts with recurrent disease whose diagnostic pathology confirmed glioblastoma multiforme will not need re-biopsy. Pts with prior low-grade glioma or WHO grade III malignant glioma are eligible if histologic assessment demonstrates transformation to GBM.
- Age > 18 years.
- Pts must be presenting in 1st, 2nd or 3rd relapse. Prior therapy must have included external beam radiotherapy.
- Adequate bone marrow, liver and renal function as assessed by following:
- An interval of at least 2 weeks between prior surgical resection (1 week for biopsy)\& initiation of study regimen;
Key exclusion criteria (16 listed)
- Prior treatment with sorafenib.
- Significant cardiac disease including any of following: a) congestive heart failure > class II NYHA; b) unstable angina (anginal symptoms at rest); c) new onset angina (within last 3 months); d) myocardial infarction within past 6 months; e) cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
- Known severe hypersensitivity to sorafenib or any of excipients or temozolomide.
- Excessive risk of bleeding as defined by stroke within prior 6 months, history of CNS or intraocular bleed, or septic endocarditis.
- Female pts who are pregnant/breast feeding, or adults of reproductive potential not employing effective method of birth control.
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 and TemozolomideAlso: Temodar, NexavarTemozolomide (50 mg per meter-squared of body surface area)every day by mouth in combination with sorafenib. Sorafenib will be taken by mouth twice every day. The dose of sorafenib will be 400 mg (2 x 200mg tablets). | Drug | Sorafenib + Temozolomide |
Primary outcome
6 Month Progression Free Survival (PFS)
Time frame: 6 months
Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
4 secondary outcomes
Safety and Toxicity of Combination
Time frame: 16 months
Pharmacokinetics: C-max
Time frame: 13 months
Pharmacokinetics: T-max
Time frame: 13 months
Pharmacokinetics: AUC-24
Time frame: 13 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20443129Reardon DA, Vredenburgh JJ, Desjardins A, Peters K, Gururangan S, Sampson JH, Marcello J, Herndon JE 2nd, McLendon RE, Janney D, Friedman AH, Bigner DD, Friedman HS. Effect of CYP3A-inducing anti-epileptics on sorafenib exposure: results of a phase II study of sorafenib plus daily temozolomide in adults with recurrent glioblastoma. J Neurooncol. 2011 Jan;101(1):57-66. doi: 10.1007/s11060-010-0217-6. Epub 2010 May 5.
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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 A Reardon, MD principal investigator
Duke Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sorafenib and Temozolomide in people with Recurrent Glioblastoma Multiforme, run by Duke University 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 18 inclusion and 16 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 24 Jun 2013. 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 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 24 Jun 2013). 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?
6 Month Progression Free Survival (PFS) (time frame: 6 months). 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 NCT00597493, 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 24 Jun 2013.