Glioblastoma MultiformePhase 2NCT00501891
Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
A Phase 2 study testing Bevacizumab and Metronomic Temozolomide in people with Glioblastoma Multiforme, run by Duke University at 1 site in United States.
Trial summary
This is a phase II study of the combination of Avastin and metronomic temozolomide in recurrent malignant glioma patients. The primary objective will be to determine the efficacy of Avastin (bevacizumab) and metronomic temozolomide in malignant glioma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Bevacizumab and Metronomic Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to Nov 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 diagnosis of WHO grade IV primary malignant glioma
- Karnofsy Performance Status (KPS) >/= 60%
- Evidence of measurable primary CNS neoplasm on contrast-enhanced MRI.
- An interval of at least 4 weeks between prior surgical resection or 1 week from a biopsy and enrollment on this protocol
- An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol.
- No evidence of CNS hemorrhage on the baseline MRI or CT scans
Who cannot join
- Life expectancy < 8 weeks
- Pregnancy or breast feeding
- Progression to metronomic temozolomide, defined as tumor progression while taking daily temozolomide or progression within 4 weeks of stopping metronomic temozolomide
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center (Brain Tumor Center)
Durham, North Carolina, 27710
About this study
Official title: A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
This is a phase II study of the combination of Avastin and metronomic temozolomide in recurrent malignant glioma patients. The primary objective will be to determine the efficacy of Avastin (bevacizumab) and metronomic temozolomide in malignant glioma patients. The secondary objective will be to determine the safety of Avastin, 10 mg/kg every other week, in combination with metronomic temozolomide in terms of progression-free survival.
Read the detailed description
This is a phase II trial of the combination of Avastin and metronomic temozolomide in recurrent WHO grade IV malignant glioma patients. Patients will receive up to 12 cycles of Avastin and temozolomide and cycles are continuous 28 days. Patients will receive daily temozolomide at a dose of 50mg/m2 and will receive Avastin every other week at a dose of 10mg/kg. Patients will be required to have a baseline MRI within 2 weeks of starting treatment and a repeat MRI every 8 weeks. A total of 32 patients will be enrolled at Duke.
Patients with recurrent malignant gliomas have a very poor prognosis, so new therapies are needed. Given the activity of metronomic temozolomide and the safety and activity of Avastin against malignant glioma, it is reasonable to study the combination in recurrent malignant glioma patients.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Bevacizumab, Metronomic Temozolomide
- Keywords
- Glioblastoma Multiforme, Brain and Central Nervous System Tumors, Recurrent Malignant Glioma, Recurrent Glioblastoma Multiforme, Avastin, Bevacizumab, Temodar, Temozolomide
- Medical subject headings
- Glioblastoma, Central Nervous System Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Bevacizumab administered intravenously 10mg/kg every other week.
Metronomic TemozolomideDrug
Also called Temodar
Temozolomide 50mg/m2 given orally on a daily basis.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab and Metronomic Temozolomide | Experimental | Patients will receive up to 12 cycles of bevacizumab (Avastin) and metronomic temozolomide (Temodar), and each cycle is 28 days. Bevacizumab will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle. Receives: Drug: Bevacizumab; Drug: Metronomic Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-Month Progression-free Survival
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. [Optional: Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).]
Measured: 6 months
Secondary outcomes (3)
Response Rate
The number of participants with complete or partial response as determined by a modification of the Macdonald criteria. Complete response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
Measured: 27 months
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage
Measured: 27 months
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity
Measured: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionDec 2007
- Study completionNov 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 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
- Not applicable
- 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
- Genentech, Inc., Schering-Plough
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00501891
- Sponsor's protocol ID
- Pro00000404
- Other IDs
- AVF3821s, P04860
- Status last verified
- Mar 2013
- First submitted
- 13 Jul 2007
- Last updated
- 27 May 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE 2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012 Mar 1;118(5):1302-12. doi: 10.1002/cncr.26381. Epub 2011 Jul 26.
PubMed 21792866
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00501891
- Acronym / sponsor ID
- Pro00000404
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma Multiforme, Brain and Central Nervous System Tumors, Recurrent Malignant Glioma, Recurrent Glioblastoma Multiforme, Avastin, Bevacizumab, Temodar, Temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., Schering-Plough
- Study start
- Jul 2007
- Primary completion
- Dec 2007 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 16 Jul 2007 (estimated)
- Results
- Posted 22 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II study of the combination of Avastin and metronomic temozolomide in recurrent malignant glioma patients. The primary objective will be to determine the efficacy of Avastin (bevacizumab) and metronomic temozolomide in malignant glioma patients. The secondary objective will be to determine the safety of Avastin, 10 mg/kg every other week, in combination with metronomic temozolomide in terms of progression-free survival.
Detailed description
This is a phase II trial of the combination of Avastin and metronomic temozolomide in recurrent WHO grade IV malignant glioma patients. Patients will receive up to 12 cycles of Avastin and temozolomide and cycles are continuous 28 days. Patients will receive daily temozolomide at a dose of 50mg/m2 and will receive Avastin every other week at a dose of 10mg/kg. Patients will be required to have a baseline MRI within 2 weeks of starting treatment and a repeat MRI every 8 weeks. A total of 32 patients will be enrolled at Duke.
Patients with recurrent malignant gliomas have a very poor prognosis, so new therapies are needed. Given the activity of metronomic temozolomide and the safety and activity of Avastin against malignant glioma, it is reasonable to study the combination in recurrent malignant glioma patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab and Metronomic Temozolomide | Experimental | Drug: Bevacizumab, Drug: Metronomic TemozolomidePatients will receive up to 12 cycles of bevacizumab (Avastin) and metronomic temozolomide (Temodar), and each cycle is 28 days. Bevacizumab will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma
- Karnofsy Performance Status (KPS) >/= 60%
- Evidence of measurable primary CNS neoplasm on contrast-enhanced MRI.
- An interval of at least 4 weeks between prior surgical resection or 1 week from a biopsy and enrollment on this protocol
- An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol.
Key exclusion criteria (4 listed)
- Life expectancy < 8 weeks
- Pregnancy or breast feeding
- Progression to metronomic temozolomide, defined as tumor progression while taking daily temozolomide or progression within 4 weeks of stopping metronomic temozolomide
- Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
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 |
|---|---|---|
| BevacizumabAlso: AvastinBevacizumab administered intravenously 10mg/kg every other week. | Drug | Bevacizumab and Metronomic Temozolomide |
| Metronomic TemozolomideAlso: TemodarTemozolomide 50mg/m2 given orally on a daily basis. | Drug | Bevacizumab and Metronomic Temozolomide |
Primary outcome
6-Month Progression-free Survival
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. [Optional: Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).]
3 secondary outcomes
Response Rate
Time frame: 27 months
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
Time frame: 27 months
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Time frame: 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21792866Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE 2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012 Mar 1;118(5):1302-12. doi: 10.1002/cncr.26381. Epub 2011 Jul 26.
- The Preston Robert Tisch Brain Tumor Center at DukeLink provided by the sponsor.
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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.
Annick Desjardins, 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 Bevacizumab and Metronomic Temozolomide in people with 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 6 inclusion and 4 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 May 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 22 Apr 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 (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 NCT00501891, 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 May 2013.