GlioblastomaPhase 2NCT00613028
Ph II Bev + Either Temozolomide/Etoposide for GBM Pts Who Have Failed Bev + Irinotecan
A Phase 2 study testing Temo + Avastin and VP-16 + Avastin in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Primary objective To estimate 6-month progression free survival probability of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety \& tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma
- What is being tested?
- Temo + Avastin and VP-16 + Avastin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Jan 2011
- 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
- Pts have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy w bev + irinotecan
- Age >18 yrs
- Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy
- Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart, /there is biopsy-proven tumor progression
- Interval of >4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.
- Eastern Cooperative Oncology Group (ECOG) 0-1
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- Hematocrit >29percent, absolute neutrophil count (ANC)>1,000 cells/ml l, platelets > 100,000 cells/ml l
- Serum creatinine<1.5 mg/dl, serum glutamate oxaloacetate transaminase (SGOT) \& bilirubin<1.5 times upper limit of normal (ULN)
- Signed informed consent approved by Institutional Review Board (IRB) prior to pt entry
- No evidence of hemorrhage on baseline MRI/CT scan other than those that are stable gr1
- If sexually active, pts will take contraceptive measures for duration of treatments
Who cannot join
- Co-medication that may interfere w study results
- Active infection requiring intravenous antibiotics
- Progression to daily etoposide/progression to daily temo
- Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide
- Requires therapeutic anti-coagulation with warfarin.
- Inability to comply w study and/or follow-up procedures
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- Current, recent,/planned participation in experimental drug study other than Genentech-sponsored bev cancer study
- Inadequately controlled hypertension
- Any prior history of hypertensive crisis/hypertensive encephalopathy
- New York Heart Association (NYHA) Gr II/greater congestive heart failure
- History of myocardial infarction (MI)/unstable angina within 6 mths prior to study enrollment
- History of stroke/transient ischemic attack within 6 mths prior to study enrollment
- Significant vascular disease
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either:
- urine protein:creatinine (UPC) ratio >1.0 at screening /
- Urine dipstick for proteinuria ≥ 2+
- Known hypersensitivity to any component of bevacizumab
- Pregnant or lactating. Use of effective means of contraception in subjects of child-bearing potential
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 II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan
Primary objective To estimate 6-month progression free survival probability of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety \& tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To evaluate radiographic response, progression free survival \& overall survival of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan
Read the detailed description
This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide \& approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I \& II error rates associated w testing are 0.030 \& 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, \& bev.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Temo + Avastin, VP-16 + Avastin
- Keywords
- Glioblastoma, Gliosarcoma, GBM, Bevacizumab, Avastin, Etoposide, Brain tumor, Irinotecan, Glioblastoma multiforme, Temodar, Temozolomide, Etopophos, Toposar, VePesid, VP-16, Camptosar
- 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.
Temo + AvastinDrug
Also called temozolomide, temodar, bevacizumab
Patients have progressed/had gr3/> toxicity related to etoposide, with no had progression/gr 3/> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day.
VP-16 + AvastinDrug
Also called VP-16, etoposide, bevacizumab, avastin
Patients have progressed/had gr3/> toxicity related to temozolomide, but have not progressed/gr3/> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Temo + Avastin | Experimental | Patients treated with bevacizumab + temozolomide Receives: Drug: Temo + Avastin |
| VP-16 + Avastin | Experimental | Patients treated with bevacizumab and VP-16 (etoposide) Receives: Drug: VP-16 + Avastin |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Outcome Measure is 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.
Measured: 6 months
Secondary outcomes (4)
Radiographic Response
Percentage of participants with an objective response (complete response or partial response) based on modified Macdonald criteria.
Measured: 41 months
Median Progression-free Survival (PFS)
Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve.
Measured: 41 months
Median Overall Survival (OS)
Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.
Measured: 41 months
Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Incidence of ≥Grade 3 treatment related, non-hematologic toxicity
Measured: 41 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2008 (estimated)
- Study startApr 2008
- Primary completionOct 2009
- Study completionJan 2011
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.
- Other trials for GlioblastomaStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- David A. Reardon, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00613028
- Sponsor's protocol ID
- Pro00003768
- Status last verified
- Jul 2013
- First submitted
- 29 Jan 2008
- Last updated
- 16 Jul 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Bevacizumab Plus Either Temozolomide or Etoposide for (GBM) Patients Who Have Failed Bevacizumab Plus Irinotecan
- ClinicalTrials.gov ID
- NCT00613028
- Acronym / sponsor ID
- Pro00003768
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, GBM, Bevacizumab, Avastin, Etoposide, Brain tumor, Irinotecan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Apr 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 12 Feb 2008 (estimated)
- Results
- Posted 4 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary objective To estimate 6-month progression free survival probability of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan Secondary Objectives To evaluate safety \& tolerability of bev + either daily temozolomide/etoposide among pts w recurrent GBM who have progressed on bev + irinotecan To evaluate radiographic response, progression free survival \& overall survival of pts w recurrent GBM treated w bev + either daily temozolomide/etoposide following progression on bev + irinotecan
Detailed description
This is exploratory, two-arm, phase II study designed to assess anti-tumor activity of bev + either daily temozolomide/etoposide among GBM pts w progressive disease following bev + irinotecan. About 48 participants w recurrent GBM will take part in this study. Approximately 24 participants will receive bev plus temozolomide \& approximately 24 will receive bev + etoposide. Pts must have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy bev + irinotecan. 24 pts will be enrolled onto each arm of this single-stage study. If 4 or more of these 24 pts live 6/more months without disease progression, treatment regimen will be considered worthy of further investigation. Otherwise, treatment regimen will be determined not worthy of further investigation within pt population. Type I \& II error rates associated w testing are 0.030 \& 0.115 respectively. Management guidelines dose reduction/interruption for temo, etoposide, \& bev.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Temo + Avastin | Experimental | Drug: Temo + AvastinPatients treated with bevacizumab + temozolomide |
| VP-16 + Avastin | Experimental | Drug: VP-16 + AvastinPatients treated with bevacizumab and VP-16 (etoposide) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Pts have confirmed diagnosis of GBM \& radiographic evidence of recurrence following prior therapy w bev + irinotecan
- Age >18 yrs
- Interval of >4 wks between prior surgical resection/1 week from stereotactic biopsy
- Interval of >12 wks from end of prior external beam radiation therapy (XRT) unless there is new area of enhancement consistent w recurrent tumor outside of XRT field,/there are progressive changes on MRI on >2 consecutive MRI scans >4wks apart, /there is biopsy-proven tumor progression
- Interval of >4 wks from prior chemo / investigational agent unless pt has recovered from all anticipated toxicities associated w that therapy.
Key exclusion criteria (24 listed)
- Co-medication that may interfere w study results
- Active infection requiring intravenous antibiotics
- Progression to daily etoposide/progression to daily temo
- Gr3/greater toxicity related to prior bev therapy,/prior temozolomide/etoposide
- Requires therapeutic anti-coagulation with warfarin.
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 |
|---|---|---|
| Temo + AvastinAlso: temozolomide, temodar, bevacizumabPatients have progressed/had gr3/> toxicity related to etoposide, with no had progression/gr 3/> toxicity related to temozolomide, will only be considered for bevacizumab and temozolomide. Bevacizumab intravenously at dose 10mg/kg every other wk. For patients on bevacizumab and temozolomide, temozolomide administered on continuous dosing schedule at 50mg/m2/day. | Drug | Temo + Avastin |
| VP-16 + AvastinAlso: VP-16, etoposide, bevacizumab, avastinPatients have progressed/had gr3/> toxicity related to temozolomide, but have not progressed/gr3/> toxicity related to etoposide,considered only for bevacizumab and etoposide. Bevacizumab intravenously at dose 10mg/kg every other wk. Patients on bevacizumab and etoposide, etoposide once daily at 50mg/m2/day first 21 days of each 28-day cycle. | Drug | VP-16 + Avastin |
Primary outcome
The Primary Outcome Measure is 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.
4 secondary outcomes
Radiographic Response
Time frame: 41 months
Median Progression-free Survival (PFS)
Time frame: 41 months
Median Overall Survival (OS)
Time frame: 41 months
Grade 3 or Greater, Treatment Related, Non-hematologic Toxicities.
Time frame: 41 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
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 Temo + Avastin and VP-16 + Avastin in people with Glioblastoma and Gliosarcoma, 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 11 inclusion and 24 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 16 Jul 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 4 Feb 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?
The Primary Outcome Measure is 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?
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 16 Jul 2013.