GliomaPhase 2NCT00795665
Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma
A Phase 2 study testing bevacizumab and carmustine in people with Glioma, run by University of California, Davis at 1 site in United States.
Trial summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma
- What is being tested?
- bevacizumab and carmustine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2008to Dec 2015
- 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
- Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma.
- Disease progression (confirmed by MRI, PET or both) after radiation therapy
- At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.
- No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer.
- Karnofsky performance score at least 70
- Platelet count ≥ 130/mm3.
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- Absolute neutrophil count ≥ 1500/mm3
- Calculated creatinine clearance greater than 45 mg/dl
- AST < 2 times the upper limit of normal
- Bilirubin < 1.5 times the upper limit of normal
- Ability to give signed informed consent
- Patients must be 18 years of age or older.
Who cannot join
- Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed.
- Evidence of CNS hemorrhage
- Requirement for therapeutic anticoagulation
- Any grade 3 or greater hemorrhage within the previous 28 days
- Active inflammatory bowel disease
- Inadequately controlled hypertension
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- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association Grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to study enrollment
- History of stroke or transient ischemic attack within 6 months 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
- Pregnant (or lactating). Use of effective means of contraception in subjects of child-bearing potential
- Prior organ transplantation
- Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
- Known acquired immune deficiency syndrome (AIDS) or HIV positive status
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with carmustine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine works in treating patients with relapsed or progressive high-grade glioma.
Read the detailed description
OBJECTIVES:
Primary
- To determine the 6-month progression-free survival of patients with relapsed or progressive high-grade gliomas treated with bevacizumab and carmustine.
Secondary
- To evaluate the radiographic response to this regimen as measured by MRI and PET scan with image fusion.
- To utilize novel brain imaging to differentiate between a radiographic response due to tumor shrinkage and a radiographic response due to decreased vasogenic edema.
- To evaluate the safety and toxicity of this regimen in these patients.
- To evaluate the overall survival of these patients.
OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4 hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months.
- Conditions
- Glioma
- Being tested
- bevacizumab, carmustine
- Keywords
- adult anaplastic astrocytoma, adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor
- Medical subject headings
- Glioma, Astrocytoma, Glioblastoma, Gliosarcoma, Oligodendroglioma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabDrug
Also called Avastin
Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.
carmustineDrug
Also called BCNU
BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab and Carmustine | Experimental | Not described Receives: Drug: bevacizumab; Drug: carmustine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).
Secondary outcomes (4)
Radiographic Response to Therapy
Response measured using MRI and PET with image fusion
Measured: One year
Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema
Measurements made by novel brain imaging
Measured: One year
Safety and Toxicity
Subjects will be assessed clinically for toxicity prior to, during, and after each infusion. NCI CTCAE 3.0 Common Terminology Criteria (CTC) for Adverse Events for toxicity and Adverse Event Reporting will be utilized.
Measured: One year
Overall Survival
Measured: Time from first day of treatment to time of death due to any cause (up to 7 years).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2015
- Study completionDec 2015
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 GliomaStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe 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
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Robert T. O'Donnell, MD, PhD, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00795665
- Sponsor's protocol ID
- 224865
- Other IDs
- UCDCC#208, P30CA093373
- Status last verified
- May 2020
- First submitted
- 20 Nov 2008
- Last updated
- 12 May 2020
- 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 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Bevacizumab (Avastin) and BCNU for Treatment of Relapsed, High Grade Gliomas
- ClinicalTrials.gov ID
- NCT00795665
- Acronym / sponsor ID
- 224865
- Conditions
- Glioma
- Keywords
- adult anaplastic astrocytoma, adult glioblastoma, adult gliosarcoma, adult giant cell glioblastoma, adult anaplastic oligodendroglioma, adult mixed glioma, recurrent adult brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Genentech, Inc.
- Study start
- Jun 2008
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 21 Nov 2008 (estimated)
- Results
- Posted 12 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with carmustine may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine works in treating patients with relapsed or progressive high-grade glioma.
Detailed description
OBJECTIVES:
Primary
- To determine the 6-month progression-free survival of patients with relapsed or progressive high-grade gliomas treated with bevacizumab and carmustine.
Secondary
- To evaluate the radiographic response to this regimen as measured by MRI and PET scan with image fusion.
- To utilize novel brain imaging to differentiate between a radiographic response due to tumor shrinkage and a radiographic response due to decreased vasogenic edema.
- To evaluate the safety and toxicity of this regimen in these patients.
- To evaluate the overall survival of these patients.
OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4 hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed every 3 months.
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 Carmustine | Experimental | Drug: bevacizumab, Drug: carmustine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma.
- Disease progression (confirmed by MRI, PET or both) after radiation therapy
- At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.
- No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer.
- Karnofsky performance score at least 70
Key exclusion criteria (22 listed)
- Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed.
- Evidence of CNS hemorrhage
- Requirement for therapeutic anticoagulation
- Any grade 3 or greater hemorrhage within the previous 28 days
- Active inflammatory bowel disease
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 (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU. | Drug | Bevacizumab and Carmustine |
| carmustineAlso: BCNUBCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU. | Drug | Bevacizumab and Carmustine |
Primary outcome
Progression-free Survival
Time frame: Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
4 secondary outcomes
Radiographic Response to Therapy
Time frame: One year
Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema
Time frame: One year
Safety and Toxicity
Time frame: One year
Overall Survival
Time frame: Time from first day of treatment to time of death due to any cause (up to 7 years).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Robert T. O'Donnell, MD, PhD principal investigator
University of California, Davis
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 carmustine in people with Glioma, run by University of California, Davis 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 12 inclusion and 22 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 May 2020. 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 12 May 2020). 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?
Progression-free Survival (time frame: Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).). 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 May 2020.