GlioblastomaPhase 2NCT00612430
Ph II Bevacizumab + Etoposide for Pts w Recurrent MG
A Phase 2 study testing Bevacizumab and Etoposide 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 patients with recurrent malignant glioma treated with Etoposide + Bevacizumab. Secondary Objectives To evaluate safety \& tolerability of Etoposide + Bevacizumab among patients with recurrent malignant glioma (RMG). 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?
- Bevacizumab and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 59 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2007to Sep 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 recurrent/progressive WHO gr III \& IV MG
- Age >18 rs
- Interval of >4 wks since prior surgery
- Interval of >4 wks since prior XRT/chemo, unless there is unequivocal evidence of progressive disease \& pts have recovered from all anticipated toxicity of most recent therapy;
- Karnofsky performance status score >60
- Hematocrit >29 percent, ANC >1,500 cells/microliter, platelets >100,000 cells/microliter
Show all 10Show fewer
- Serum creatinine <1.5 mg/dl, BUN <25 mg/dl, serum SGOT \& bilirubin <1.5 x ULN
- For pts on corticosteroids, they have been on astable dose for 1wk prior to entry
- Signed informed consent approved by IRB prior to pt entry
- If sexually active, pts must agree to take contraceptive measures for duration of treatments.
Who cannot join
- Prior therapy w either bevacizumab/etoposide
- >3 prior recurrences
- Pregnancy/breast feeding
- Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
- Evidence of CNS hemorrhage on baseline MRI on CT scan
- Pts who require therapeutic anti-coagulation
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance w study requirements, or disorders associated w significant immunocompromised state
- Pts w another primary malignancy that has required treatment <past year
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 Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma
Primary Objective to estimate 6-month progression free survival probability of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
Secondary Objectives To evaluate safety \& tolerability of Etoposide + Bevacizumab among patients with recurrent malignant glioma (RMG).
To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
Read the detailed description
Exploratory, single-arm, ph II study designed to assess anti-tumor activity of combinatorial regimen consisting of Etoposide + Bevacizumab among patients with RMG. Primary endpoint of study is probability of progression-free survival at 6 months. Important secondary objective is to further assess safety of Etoposide \& Bevacizumab for patients with recurrent malignant glioma.
If study demonstrates that combinatorial regimen of Etoposide + Bevacizumab is associated with encouraging anti-tumor activity among patients with RMG, further assessment of regimen in additional phase II \& possibly phase III studies, will be considered.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Bevacizumab and Etoposide
- Keywords
- Glioblastoma, Gliosarcoma, GBM, MG, Brain tumor, Bevacizumab, Avastin, Etoposide, VP-16, Etopophos, Toposar, VePesid, Glioblastoma multiforme, Recurrent GBM, Anaplastic astrocytoma, Malignant glioma
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms, Astrocytoma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bevacizumab and EtoposideDrug
Also called Bevacizumab - Avastin, Etoposide-Etopophos-Toposar-VePesid-VP-16
32 pts w recurrent WHO grade III MG \& 27 pts w recurrent WHO grade IV MG will be enrolled in this study. Estimated rate of accrual is 10 pts per month. The estimated date of study completion is 6-9 months from study initiation. Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If pt tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. The Duke investigators will review all la data \& order treatment. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab + Etoposide | Experimental | Grade III and IV patients will receive: Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If patient tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. Receives: Drug: Bevacizumab and Etoposide |
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. Progression was defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans.
Measured: 6 months
Secondary outcomes (4)
Objective Response Rate
The percentage of participants with complete or partial response as determined by the following 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; 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. A confirmation of response was not required.
Measured: 2 years
Safety of Study Treatment Regimen
Number of participants experiencing a non-hematologic toxicity ≥ grade 3 that was possibly, probably, or definitely related to study treatment.
Measured: 2 years
Median Progression-Free Survival
Time in weeks from the start of study treatment to the date of first progression, 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: Patients were followed for a median of 91.4 weeks
Median Overall Survival (OS)
Time in weeks 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: median of 91.4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startMar 2007
- Primary completionSep 2008
- Study completionSep 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.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 59 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
- NCT00612430
- Sponsor's protocol ID
- Pro00000379
- Status last verified
- May 2013
- First submitted
- 29 Jan 2008
- Last updated
- 12 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer. 2009 Dec 15;101(12):1986-94. doi: 10.1038/sj.bjc.6605412. Epub 2009 Nov 17.
PubMed 19920819
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Bevacizumab Plus Etoposide for Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00612430
- Acronym / sponsor ID
- Pro00000379
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, GBM, MG, Brain tumor, Bevacizumab, Avastin, Etoposide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 59 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Mar 2007
- Primary completion
- Sep 2008 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 26 Jul 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 patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
Secondary Objectives To evaluate safety \& tolerability of Etoposide + Bevacizumab among patients with recurrent malignant glioma (RMG).
To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with Etoposide + Bevacizumab.
Detailed description
Exploratory, single-arm, ph II study designed to assess anti-tumor activity of combinatorial regimen consisting of Etoposide + Bevacizumab among patients with RMG. Primary endpoint of study is probability of progression-free survival at 6 months. Important secondary objective is to further assess safety of Etoposide \& Bevacizumab for patients with recurrent malignant glioma.
If study demonstrates that combinatorial regimen of Etoposide + Bevacizumab is associated with encouraging anti-tumor activity among patients with RMG, further assessment of regimen in additional phase II \& possibly phase III studies, will be considered.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab + Etoposide | Experimental | Drug: Bevacizumab and EtoposideGrade III and IV patients will receive: Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If patient tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Pts have confirmed diagnosis of recurrent/progressive WHO gr III \& IV MG
- Age >18 rs
- Interval of >4 wks since prior surgery
- Interval of >4 wks since prior XRT/chemo, unless there is unequivocal evidence of progressive disease \& pts have recovered from all anticipated toxicity of most recent therapy;
- Karnofsky performance status score >60
Key exclusion criteria (8 listed)
- Prior therapy w either bevacizumab/etoposide
- >3 prior recurrences
- Pregnancy/breast feeding
- Co-medication w immuno-suppressive agents other than corticosteroids including but not limited to cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil
- Evidence of CNS hemorrhage on baseline MRI on CT scan
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 |
|---|---|---|
| Bevacizumab and EtoposideAlso: Bevacizumab - Avastin, Etoposide-Etopophos-Toposar-VePesid-VP-1632 pts w recurrent WHO grade III MG \& 27 pts w recurrent WHO grade IV MG will be enrolled in this study. Estimated rate of accrual is 10 pts per month. The estimated date of study completion is 6-9 months from study initiation. Bevacizumab administered intravenously at dose 10 mg/kg every two weeks. If pt tolerates 1st bevacizumab dose, subsequent doses may be given by local oncologists under direct supervision of Duke investigators. Etoposide administered orally, once daily for 1st 21 days of each 28-day treatment cycle. Dose of Etoposide will be 50 mg/m2/day. The Duke investigators will review all la data \& order treatment. Treatment will continue until either evidence of progressive disease, unacceptable toxicity, non-compliance w study follow-up, or withdrawal of consent. | Drug | Bevacizumab + Etoposide |
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. Progression was defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans.
4 secondary outcomes
Objective Response Rate
Time frame: 2 years
Safety of Study Treatment Regimen
Time frame: 2 years
Median Progression-Free Survival
Time frame: Patients were followed for a median of 91.4 weeks
Median Overall Survival (OS)
Time frame: median of 91.4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 19920819Reardon DA, Desjardins A, Vredenburgh JJ, Gururangan S, Sampson JH, Sathornsumetee S, McLendon RE, Herndon JE 2nd, Marcello JE, Norfleet J, Friedman AH, Bigner DD, Friedman HS. Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study. Br J Cancer. 2009 Dec 15;101(12):1986-94. doi: 10.1038/sj.bjc.6605412. Epub 2009 Nov 17.
- The Preston Robert Tisch Brain Tumor Center at DUKELink provided by the sponsor.
Related trials for Glioblastoma
Active, not recruitingPhase 3
EF-41/KEYNOTE D58: Phase 3 Study of Optune Concomitant With Temozolomide Plus Pembrolizumab in Newly Diagnosed Glioblastoma
Glioblastoma
RecruitingPhase 3
Beginning Radiation Immediately With GammaTile at GBM Excision Versus Standard of Care
Glioblastoma
RecruitingPhase 1/2
Testing the Addition of an Anti-cancer Drug, Selinexor, to the Usual Chemotherapy Treatment (Temozolomide) for Brain Tumors That Have Returned After Previous Treatment
Recurrent Glioblastoma, IDH-Wildtype, Recurrent MGMT-Methylated Glioblastoma
Active, not recruitingPhase 1
Oral Gallium Maltolate for the Treatment of Relapsed and Refractory Glioblastoma
Glioblastoma
RecruitingPhase 1/2
PLX038 in Primary Central Nervous System Tumors Containing MYC or MYCN Amplifications
Glioma, Medulloblastoma
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 Bevacizumab and Etoposide 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 10 inclusion and 8 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 12 Aug 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 26 Jul 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 NCT00612430, 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 12 Aug 2013.