GlioblastomaPhase 2NCT00597402
Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas
A Phase 2 study testing Avastin, Temozolomide and Radiation Therapy (XRT) in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Gliosarcoma, Brain Tumor
- What is being tested?
- Avastin, Temozolomide and Radiation Therapy (XRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 125 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2007to May 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 must have histologically confirmed diagnosis of World Health Organization (WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 4 weeks of the last major surgical procedure.
- Age > 18 years.
- An interval of at least 2 weeks and not > 6 weeks between prior major surgical procedure and study enrollment.
- No prior radiotherapy or chemotherapy for a brain tumor
- Karnofsky ≥ 60 percent.
- Hemoglobin ≥ 9.0 g/deciliter (dl), absolute neutrophil count (ANC) ≥ 1,500 cells/ microliter, platelets ≥ 125,000 cells/microliter.
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- Serum creatinine ≤ 1.5 mg/dl, serum serum glutamic-oxaloacetic transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal (ULN).
- For patients on corticosteroids, they must be on a stable or decreasing dose for 1 week prior to entry, and the dose should not be escalated over entry dose level, if clinically possible.
- Signed informed consent approved by the Institutional Review Board
- No evidence of > grade 1 central nervous system (CNS) hemorrhage on the baseline MRI or CT scan.
- If sexually active, patients will take contraceptive measures for the duration of treatment as stated in the informed consent.
Who cannot join
- Pregnancy or breast feeding.
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
- Active infection requiring intravenous (IV) antibiotics.
- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
- Evidence of > grade 1 CNS hemorrhage on baseline MRI on CT scan.
- Avastin-Specific Concerns:
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- Subjects meeting any of the following criteria are ineligible for study entry:
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study
- Blood pressure of 150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) Grade II or greater 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 (prothrombin time (PT) or partial thromboplastin time (PTT) >1.5x normal or a history of > three grade 2 or greater hemorrhages)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to first Avastin infusion during XRT/Temodar or anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to first Avastin infusion during XRT/Temodar
- Pregnant (positive pregnancy test) or lactating
- Urine protein >1.0 + at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to first Avastin infusion during XRT/Temodar
- Serious, non-healing wound, ulcer, or bone fractures.
- 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: Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas
Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection.
Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Read more
Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Read the detailed description
The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high O(6)-methylguanine-DNA methyltransferase (MGMT), conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal immunoglobulin G (IGG) 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed glioblastoma (GBM) patients, including a Radiation Therapy Oncology Group (RTOG) study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a University of California, Los Angeles (UCLA) study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.
- Conditions
- Glioblastoma, Gliosarcoma, Brain Tumor
- Being tested
- Avastin, Temozolomide, Radiation Therapy (XRT), Irinotecan
- Keywords
- Avastin, Bevacizumab, Temozolomide, Temodar, Irinotecan, Camptosar, GBM, Glioblastoma Multiforme, Gliosarcoma, Brain tumor, Glioma, New GBM, Newly diagnosed GBM or gliosarcoma malignant brain tumor
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AvastinDrug
Also called Bevacizumab
Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive treatment that includes 6 cycles of Avastin, beginning a minimum of 14 days after last XRT.
TemozolomideDrug
Also called Temodar
Daily temozolomide 75 mg/m2/day for 6.5 weeks of radiation treatment. Following completion of XRT, patients will receive treatment including temozolomide 200 mg/m2/day on the 1st 5 days of each 28-day cycle.
Radiation Therapy (XRT)Radiation
Treatment with standard XRT (radiation) for 6.5 weeks.
IrinotecanDrug
Also called CPT-11, Camptosar
Following completion of XRT, patients will receive 6 cycles of treatment that includes irinotecan. Beginning a minimum of 14 days after last XRT, the irinotecan dose will depend on whether the patient is on enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED: 125 mg/m2.)
| Study group | Role | What they receive |
|---|---|---|
| Avastin, radiation, temozolomide, and irinotecan | Experimental | Not described Receives: Drug: Avastin; Drug: Temozolomide; Radiation: Radiation Therapy (XRT); Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
16-month Overall Survival (OS)
Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.
Measured: 16 months
Secondary outcomes (3)
12-month Progression-free Survival (PFS)
Percentage of participants surviving twelve 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: 12 months
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage
Number of times a CNS hemorrhage or systemic hemorrhage was experienced
Measured: 55 months
Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Number of times a grade ≥ 4 hematologic or grade ≥ 3 non-hematologic toxicity was experienced
Measured: 55 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 startJul 2007
- Primary completionAug 2011
- Study completionMay 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
- Single group
- Masking
- None (open label)
- Enrolment
- 125 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, FRCPC, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00597402
- Sponsor's protocol ID
- Pro00000458
- Status last verified
- Apr 2014
- First submitted
- 10 Jan 2008
- Last updated
- 7 May 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 7 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas
- ClinicalTrials.gov ID
- NCT00597402
- Acronym / sponsor ID
- Pro00000458
- Conditions
- Glioblastoma, Gliosarcoma, Brain Tumor
- Keywords
- Avastin, Bevacizumab, Temozolomide, Temodar, Irinotecan, Camptosar, GBM, Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., Schering-Plough
- Study start
- Jul 2007
- Primary completion
- Aug 2011 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 18 Jan 2008 (estimated)
- Results
- Posted 18 Jan 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 use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection.
Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Detailed description
The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high O(6)-methylguanine-DNA methyltransferase (MGMT), conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal immunoglobulin G (IGG) 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed glioblastoma (GBM) patients, including a Radiation Therapy Oncology Group (RTOG) study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a University of California, Los Angeles (UCLA) study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avastin, radiation, temozolomide, and irinotecan | Experimental | Drug: Avastin, Drug: Temozolomide, Radiation: Radiation Therapy (XRT), Drug: Irinotecan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically confirmed diagnosis of World Health Organization (WHO) grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 4 weeks of the last major surgical procedure.
- Age > 18 years.
- An interval of at least 2 weeks and not > 6 weeks between prior major surgical procedure and study enrollment.
- No prior radiotherapy or chemotherapy for a brain tumor
- Karnofsky ≥ 60 percent.
Key exclusion criteria (23 listed)
- Pregnancy or breast feeding.
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
- Active infection requiring intravenous (IV) antibiotics.
- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
- Evidence of > grade 1 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 |
|---|---|---|
| AvastinAlso: BevacizumabAvastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive treatment that includes 6 cycles of Avastin, beginning a minimum of 14 days after last XRT. | Drug | Avastin, radiation, temozolomide, and irinotecan |
| TemozolomideAlso: TemodarDaily temozolomide 75 mg/m2/day for 6.5 weeks of radiation treatment. Following completion of XRT, patients will receive treatment including temozolomide 200 mg/m2/day on the 1st 5 days of each 28-day cycle. | Drug | Avastin, radiation, temozolomide, and irinotecan |
| Radiation Therapy (XRT)Treatment with standard XRT (radiation) for 6.5 weeks. | Radiation | Avastin, radiation, temozolomide, and irinotecan |
| IrinotecanAlso: CPT-11, CamptosarFollowing completion of XRT, patients will receive 6 cycles of treatment that includes irinotecan. Beginning a minimum of 14 days after last XRT, the irinotecan dose will depend on whether the patient is on enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED: 125 mg/m2.) | Drug | Avastin, radiation, temozolomide, and irinotecan |
Primary outcome
16-month Overall Survival (OS)
Time frame: 16 months
Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.
3 secondary outcomes
12-month Progression-free Survival (PFS)
Time frame: 12 months
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage
Time frame: 55 months
Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Time frame: 55 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 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.
Annick Desjardins, MD, FRCPC 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, Temozolomide and Radiation Therapy (XRT) 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 23 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 7 May 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 18 Jan 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?
16-month Overall Survival (OS) (time frame: 16 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 7 May 2014.