GlioblastomaPhase 2NCT00612339
Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas
A Phase 2 study testing Avastin and Temozolomide in people with Glioblastoma and Gliosarcoma, run by Duke University at 1 site in United States.
Trial summary
Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate. Secondary objective- To determine safety of Avastin \& Temozolomide in unresectable glioblastoma patients 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 Temozolomide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to May 2012
- 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 WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease.
- Age ≥ 18years \& life expectancy of >12 weeks
- Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
- Interval of <1 week between prior biopsy/4 weeks from surgical resection \& enrollment on protocol
- Karnofsky ≥60%
- Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter
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- Serum creatinine ≤1.5 mg/dl, serum SGOT \& bilirubin ≤1.5 x ULN
- For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, \& dose should not be escalated over entry dose level
- Signed informed consent approved by IRB prior to patient entry
- No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan
- If sexually active, patients will take contraceptive measures for duration of treatments
Who cannot join
- Pregnancy/breast feeding
- Co-medication that may interfere with study results
- Active infection requiring IV antibiotics
- Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor
- Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan
- Avastin-Specific Concerns:
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- Inadequately controlled hypertension
- Any prior history of hypertensive crisis/hypertensive encephalopathy
- New York Heart Association Grade II or > congestive heart failure
- History of myocardial infarction/unstable angina < 6 months prior to study enrollment
- History of stroke/transient ischemic attack < 6 months prior to study enrollment
- Significant vascular disease
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis/coagulopathy
- Major surgical procedure, open biopsy,/significant traumatic injury within 28 days prior to study enrollment/anticipation of need for major surgical procedure during course of study
- Core biopsy/other minor surgical procedure, excluding placement of vascular access device, <7 days prior to study enrollment
- History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by either
- UPC ratio ≥1.0 at screening OR
- Urine dipstick for proteinuria ≥2+
- Known hypersensitivity to any component of Avastin
- Pregnant/lactating. Use of effective means of contraception in subjects of child-bearing potential
- Current, ongoing treatment with full-dose warfarin or its equivalent
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 Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.
Secondary objective- To determine safety of Avastin \& Temozolomide in unresectable glioblastoma patients
Read the detailed description
Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin \& Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin \& Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I \& II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, \& hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, \& arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.
- Conditions
- Glioblastoma, Gliosarcoma
- Being tested
- Avastin and Temozolomide
- Keywords
- Glioma, Temozolomide, Temodar, Avastin, Bevacizumab, GBM, Gliosarcoma, Multifocal GBM, Brain tumor, Unresectable GBM, Glioblastoma multiforme
- 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.
Avastin and TemozolomideDrug
Also called Avastin - Bevacizumab, Temozolomide - Temodar
This is Phase II study with the combination of Avastin \& Temozolomide for unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up to 4 cycles of Avastin \& Temozolomide . Avastin administered at 10 mg/kg every 14 days beginning minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide will be dosed at 200 mg/m2 daily x 5 days in 28-day cycle. Patients will have baseline MRI \& repeat MRI every 4 weeks. If there is no evidence of disease progression after each cycle, or unacceptable toxicity, or as determined by investigators, patient non-compliance or patient withdraws consent to continue therapy \& requests discontinuation, patients will receive up to 4 cycles of Avastin \& Temozolomide, then proceed with standard XRT therapy, \& future therapy after 4 cycles will be at discretion of patient \& treating physicians.
| Study group | Role | What they receive |
|---|---|---|
| Avastin and Temozolomide | Experimental | Avastin administered at 10 mg/kg every 2 weeks beginning a minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in a 28-day cycle. Receives: Drug: Avastin and Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. 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, and maintained for at least 4 weeks. 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, and maintained for at least 4 weeks.
Measured: 4 months
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 startAug 2007
- Primary completionMay 2012
- Study completionMay 2012
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Schering-Plough
- Responsible party
- Sponsor
- Investigators
- Katherine B Peters, MD, PhD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00612339
- Sponsor's protocol ID
- Pro00001022
- Status last verified
- Sep 2012
- First submitted
- 29 Jan 2008
- Last updated
- 27 May 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 27 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas
- ClinicalTrials.gov ID
- NCT00612339
- Acronym / sponsor ID
- Pro00001022
- Conditions
- Glioblastoma, Gliosarcoma
- Keywords
- Glioma, Temozolomide, Temodar, Avastin, Bevacizumab, GBM, Gliosarcoma, Multifocal GBM
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., Schering-Plough
- Study start
- Aug 2007
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 10 Sep 2012
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 determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.
Secondary objective- To determine safety of Avastin \& Temozolomide in unresectable glioblastoma patients
Detailed description
Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin \& Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin \& Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I \& II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, \& hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, \& arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Avastin and Temozolomide | Experimental | Drug: Avastin and TemozolomideAvastin administered at 10 mg/kg every 2 weeks beginning a minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in a 28-day cycle. |
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 have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease.
- Age ≥ 18years \& life expectancy of >12 weeks
- Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
- Interval of <1 week between prior biopsy/4 weeks from surgical resection \& enrollment on protocol
- Karnofsky ≥60%
Key exclusion criteria (24 listed)
- Pregnancy/breast feeding
- Co-medication that may interfere with study results
- Active infection requiring IV antibiotics
- Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor
- Evidence of > grade 1 CNS hemorrhage on baseline MRI or 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 |
|---|---|---|
| Avastin and TemozolomideAlso: Avastin - Bevacizumab, Temozolomide - TemodarThis is Phase II study with the combination of Avastin \& Temozolomide for unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up to 4 cycles of Avastin \& Temozolomide . Avastin administered at 10 mg/kg every 14 days beginning minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide will be dosed at 200 mg/m2 daily x 5 days in 28-day cycle. Patients will have baseline MRI \& repeat MRI every 4 weeks. If there is no evidence of disease progression after each cycle, or unacceptable toxicity, or as determined by investigators, patient non-compliance or patient withdraws consent to continue therapy \& requests discontinuation, patients will receive up to 4 cycles of Avastin \& Temozolomide, then proceed with standard XRT therapy, \& future therapy after 4 cycles will be at discretion of patient \& treating physicians. | Drug | Avastin and Temozolomide |
Primary outcome
Response Rate
Time frame: 4 months
The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. 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, and maintained for at least 4 weeks. 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, and maintained for at least 4 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 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.
Katherine B Peters, MD, PhD 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 Temozolomide 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 27 May 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 10 Sep 2012). 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?
Response Rate (time frame: 4 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 27 May 2013.