GlioblastomaPhase 2NCT00611325
Phase II Avastin + Bortezomib for Patients With Recurrent Malignant Glioma
A Phase 2 study testing Avastin and Bortezomib 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 glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs. 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?
- Avastin and Bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteUnited States
- Study dates
- May 2008to Oct 2013
- 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 have histologically confirmed diagnosis of recurrent/progressive WHO grade IV malignant glioma (MG)
- Age >18 yrs
- No prior treatment with bortezomib, \& no Avastin in last 3 months, not allowed to have progressed to Avastin regimen. No history of > or equal to grade 2 CNS hemorrhage or grade 3 or higher toxicities while on Avastin
- At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy \& enrollment in this study
- Karnofsky Performance Status (KPS) > or equal to 70%
- Hemoglobin (Hgb) > or = to 9 g/deciliter (dL), absolute neutrophil count (ANC) > or = to 1,500 cells/microliter, platelets > or = to 125,000 cells/microliter;
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- Serum creatinine <1.5 mg/dL, serum glutamic oxalocetic transaminase (SGOT) \& bilirubin <1.5 x upper limit of normal
- Signed informed consent approved by IRB;
- If sexually active, patients must agree to take contraceptive measures for duration of treatments
- May have had up to 3 biological therapies (such as tyrosine kinase inhibitors, topoisomerase I or II inhibitors, or rapamycin)
Who cannot join
- Gr 2 or greater peripheral neuropathy at time of study enrollment
- No prior taxanes, as it predisposes to sensory neuropathy
- Co-medication that may interfere with study results, e.g. immuno-suppressive agents other than corticosteroids
- Greater than 3 prior recurrences
- Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months)
- History of thrombotic or hemorrhagic stroke or myocardial infarction within 6 months
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- Requires therapeutic anti-coagulation
- At least 4 weeks from Day 0 of prior monthly chemotherapy (at least 6 weeks if a nitrosourea). At least 1 week from last dose of daily chemotherapy (such as metronomic temozolomide, cytoxan) or targeted therapies administered daily (such as gleevec, tarceva)
- Pregnancy or breast feeding
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring IV antibiotics \& psychiatric illness/social situations that would limit compliance with study requirements, or disorders associated with significant immunocompromised state
- Patients with another primary malignancy that has required treatment within past year.
- Avastin-Specific Concerns:
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- Systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg
- Unstable angina
- New York Heart Association Gr II or > congestive heart failure
- History of myocardial infarction within 6 months
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- Evidence of bleeding diathesis, coagulopathy as documented by an elevated prothrombin time (PT), partial thromboplastin time (PTT)/bleeding time
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during course of study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0
- Urine protein: creatinine ratio > or = to 1.0 at screening
- History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months prior to Day 0
- Serious, non-healing wound, ulcer, or bone fracture
- Known hypersensitivity to any component of Avastin
- Inability to comply with study and/or follow-up procedures
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 Avastin Plus Bortezomib for Patients With Recurrent Malignant Glioma
Primary Objective To estimate 6-month progression free survival probability of patients with recurrent glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs.
Secondary Objectives To evaluate safety \& tolerability of bortezomib plus Avastin among patients with recurrent malignant glioma.
To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with bortezomib plus Avastin
Read the detailed description
This is an open-label, 2-arm Phase II study assessing safety \& efficacy of bortezomib in combination with Avastin for patients with recurrent glioblastoma multiforme (gbm). 56 total patients with recurrent WHO grade IV malignant gliomas have been enrolled on study. Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. The dose of bortezomib was 1.7 mg/m2 for non-EIAED patients \& 2.5 mg/m2 for EIAED patients. Treatment continued until either evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up / withdrawal of consent. Brain MRIs were obtained after every cycle.
Bortezomib administration is associated with mild toxicity in most patients, such as fatigue, diarrhea \& nausea, constipation \& peripheral neuropathy. Less common, bortezomib administration leads to more significant hematologic toxicities \& peripheral neuropathies. Most significant toxicities associated with Avastin in recently completed phase II clinical trial at Duke were thrombotic complications \& grade 2 proteinuria. "Unacceptable" toxicities rates of 15 percent or less were considered desirable, while rates of 40 percent or greater were considered undesirable. The statistical hypothesis that needed testing differentiated between 15% \& 40% rate of unacceptable toxicity.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Avastin, Bortezomib
- Keywords
- Glioblastoma, Gliosarcoma, Glioblastoma multiforme, Recurrent malignant glioma, GBM, Recurrent GBM, Malignant glioma, Brain tumor, Avastin, Bevacizumab, Bortezomib, Velcade
- Medical subject headings
- Glioblastoma, Gliosarcoma, Glioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvastinDrug
Also called Bevacizumab
Avastin was administered intravenously at the dose 15 mg/kg every 3 weeks.
BortezomibDrug
Also called Velcade
Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. Bortezomib was 1.7 mg/m2 for patients not taking EIAEDs \& 2.5 mg/m2 for patients taking EIAEDs.
| Study group | Role | What they receive |
|---|---|---|
| EIAED | Experimental | Patients taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 2.5 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle. Receives: Drug: Avastin; Drug: Bortezomib |
| Non-EIAED | Experimental | Patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 1.7 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle. Receives: Drug: Avastin; Drug: Bortezomib |
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 initiation of treatment without progression of disease. PFS was defined as the time from the initiation of treatment to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. Per Macdonald, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
Measured: 6 months
Secondary outcomes (4)
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. Per Macdonald, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion, or clinical deterioration. 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: Time in months from the start of study treatment to the date of first progression or death. Assessed up to 60 months.
Median Overall Survival (OS)
Time in months from the start of study treatment to the date of death. 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: Time in months from the start of study treatment to date of death due to any cause. Assessed up to 60 months.
Radiographic Response Rate
The percentage of participants with a complete or partial response at any assessment as determined by the Macdonald criteria. A confirmation of response was not required. Per Macdonald criteria, complete response (CR) was the disappearance of all target lesions and partial response (PR) was a ≥50% decrease in the sum of the longest diameter of target lesions, no new lesions and stable or decreasing steroid dose. Objective response =CR+PR. Tumor assessments were done at baseline and at the end of each 6 week treatment cycle, and overall best response was recorded.
Measured: 60 months
Number of Patients With Grade 3 or Greater, Treatment-related, Non-hematologic Toxicities
Number of patients with grade 3 or greater, treatment-related, non-hematologic toxicities based on Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2008 (estimated)
- Study startMay 2008
- Primary completionSep 2009
- Study completionOct 2013
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
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Katherine B Peters, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611325
- Sponsor's protocol ID
- Pro00003596
- Status last verified
- Feb 2014
- First submitted
- 28 Jan 2008
- Last updated
- 12 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Avastin Plus Bortezomib for Patients With Recurrent Malignant Glioma
- ClinicalTrials.gov ID
- NCT00611325
- Acronym / sponsor ID
- Pro00003596
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioblastoma, Gliosarcoma, Glioblastoma multiforme, Recurrent malignant glioma, GBM, Recurrent GBM, Malignant glioma, Brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc., Genentech, Inc.
- Study start
- May 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 8 Feb 2008 (estimated)
- Results
- Posted 4 Feb 2014
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 glioblastoma multiforme treated with bortezomib plus Avastin. This efficacy assessment will be made separately among patients on enzyme-inducing anti-epileptic drugs and non enzyme-inducing anti-epileptic drugs.
Secondary Objectives To evaluate safety \& tolerability of bortezomib plus Avastin among patients with recurrent malignant glioma.
To evaluate radiographic response, progression free survival \& overall survival of patients with recurrent malignant glioma treated with bortezomib plus Avastin
Detailed description
This is an open-label, 2-arm Phase II study assessing safety \& efficacy of bortezomib in combination with Avastin for patients with recurrent glioblastoma multiforme (gbm). 56 total patients with recurrent WHO grade IV malignant gliomas have been enrolled on study. Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. The dose of bortezomib was 1.7 mg/m2 for non-EIAED patients \& 2.5 mg/m2 for EIAED patients. Treatment continued until either evidence of progressive disease, unacceptable toxicity, non-compliance with study follow-up / withdrawal of consent. Brain MRIs were obtained after every cycle.
Bortezomib administration is associated with mild toxicity in most patients, such as fatigue, diarrhea \& nausea, constipation \& peripheral neuropathy. Less common, bortezomib administration leads to more significant hematologic toxicities \& peripheral neuropathies. Most significant toxicities associated with Avastin in recently completed phase II clinical trial at Duke were thrombotic complications \& grade 2 proteinuria. "Unacceptable" toxicities rates of 15 percent or less were considered desirable, while rates of 40 percent or greater were considered undesirable. The statistical hypothesis that needed testing differentiated between 15% \& 40% rate of unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EIAED | Experimental | Drug: Avastin, Drug: BortezomibPatients taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 2.5 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle. |
| Non-EIAED | Experimental | Drug: Avastin, Drug: BortezomibPatients not taking enzyme-inducing anti-epileptic drugs (EIAEDs). Avastin was administered intravenously at a dose of 15 mg/kg every 3 weeks. Bortezomib was adminstered intravenously at a dose of 1.7 mg/m2 on days 1, 4, 8, 11, 22, 25, 29, and 32 of a 42-day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients have histologically confirmed diagnosis of recurrent/progressive WHO grade IV malignant glioma (MG)
- Age >18 yrs
- No prior treatment with bortezomib, \& no Avastin in last 3 months, not allowed to have progressed to Avastin regimen. No history of > or equal to grade 2 CNS hemorrhage or grade 3 or higher toxicities while on Avastin
- At least 6 weeks from surgical resection, 4 weeks from end of radiotherapy \& enrollment in this study
- Karnofsky Performance Status (KPS) > or equal to 70%
Key exclusion criteria (27 listed)
- Gr 2 or greater peripheral neuropathy at time of study enrollment
- No prior taxanes, as it predisposes to sensory neuropathy
- Co-medication that may interfere with study results, e.g. immuno-suppressive agents other than corticosteroids
- Greater than 3 prior recurrences
- Evidence of CNS hemorrhage on baseline MRI on CT scan (except for grade 1 hemorrhage that has been stable for at least 3 months)
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 |
|---|---|---|
| AvastinAlso: BevacizumabAvastin was administered intravenously at the dose 15 mg/kg every 3 weeks. | Drug | EIAED, Non-EIAED |
| BortezomibAlso: VelcadeBortezomib was administered on days 1, 4, 8, 11, 22, 25, 29, \& 32 of a 42-day cycle. Bortezomib was 1.7 mg/m2 for patients not taking EIAEDs \& 2.5 mg/m2 for patients taking EIAEDs. | Drug | EIAED, Non-EIAED |
Primary outcome
6-month Progression-free Survival (PFS)
Time frame: 6 months
Percentage of participants surviving six months from the initiation of treatment without progression of disease. PFS was defined as the time from the initiation of treatment to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. Per Macdonald, progression is a ≥ 25% increase in the sum of the products of perpendicular diameters of enhancing lesions, any new lesion or clinical deterioration.
4 secondary outcomes
Median Progression Free Survival (PFS)
Time frame: Time in months from the start of study treatment to the date of first progression or death. Assessed up to 60 months.
Median Overall Survival (OS)
Time frame: Time in months from the start of study treatment to date of death due to any cause. Assessed up to 60 months.
Radiographic Response Rate
Time frame: 60 months
Number of Patients With Grade 3 or Greater, Treatment-related, Non-hematologic Toxicities
Time frame: 60 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2014.
- 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.
Katherine B Peters, 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 Avastin and Bortezomib 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 27 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 Mar 2014. 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 2014). 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?
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 Mar 2014.