Malignant GliomaPhase 2NCT01004874
Avastin/Radiation (XRT)/Temozolomide (Temodar) Followed by Avastin/Temodar/Topotecan for Glioblastoma
A Phase 2 study testing Bevacizumab, Temozolomide and Radiation Therapy (XRT) in people with Malignant Glioma and Glioblastoma, run by Duke University at 1 site in United States.
Trial summary
This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Glioblastoma, Gliosarcoma
- What is being tested?
- Bevacizumab, 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
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Dec 2009to 2 Nov 2021
- 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 WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 6 weeks of the last major surgical procedure.
- Age > or = to 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 > or = to 60%.
- Hemoglobin ≥ 9.0 g/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 glutamic oxaloacetic transaminase (SGOT) and bilirubin ≤ 1.5 times upper limit of normal.
- Signed informed consent approved by the Institutional Review Board
- If sexually active, patients must agree to use appropriate contraceptive measures for the duration of the study and for 6 months afterwards 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 IV antibiotics.
- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
- Evidence of > grade 1 central nervous system (CNS) hemorrhage on baseline MRI on CT scan.
- Avastin-specific Exclusion Criteria:
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- Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) 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 (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study enrollment
- History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to study enrollment
- Evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
- 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 within 6 months prior to study enrollment
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Proteinuria at screening as demonstrated by either urine protein:creatinine (UPC) ratio ≥ 1.0 at screening OR urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24-hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of Avastin
- Pregnant (positive pregnancy test) or lactation. Use of effective means of contraception (men and women) in subjects of child-bearing potential
Trial locations and contacts
1 site in 1 country.
United States1 site
The Preston Robert Tisch Brain Tumor Center at Duke
Durham, North Carolina, 27710
About this study
Official title: Avastin in Combination With Radiation and Temozolomide Followed by Avastin, Temozolomide, and Topotecan for Glioblastoma Multiformes and Gliosarcomas
This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.
Read the detailed description
The primary objective of this study is to use 6-month progression-free survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objectives are to determine the overall survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan and to describe the toxicity of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan.
The study will have survival and toxicity endpoints. Patients will be treated with standard radiation therapy and daily temozolomide for 6 and a half weeks of radiation. Avastin will be administered every other week beginning a minimum of 28 days after the last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of radiation therapy, patients will have a MRI and if there is no evidence of disease progression, patients will receive 12 cycles of Avastin, temozolomide, and topotecan (beginning a minimum of 14 days after the last radiation treatment). Subjects will be identified by the investigator as those patients who have newly diagnosed grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma), and be within 6 weeks of the last major surgical procedure, craniotomy, open biopsy, or stereotactic biopsy.
Fifty (50) patients will initially be accrued to the study and the overall efficacy of the treatment regimen assessed. Analyses will be conducted within subgroups defined by methylation status.
Early side effects of radiation that may start during radiation include hair loss, scalp redness, inflammation of the ear canals, and fatigue. There is a small chance of long-term effects from radiation, occurring after months or years after completion. These may include worsening of mental function, hearing, vision, strength and coordination. In initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. Temozolomide has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, and hepatotoxicity. With topotecan, reversible myelosuppression with leukopenia and thrombocytopenia is dose limiting. Nausea and vomiting, as well as diarrhea and alopecia, are frequent. Moderate fatigue, transient elevation of hepatic transaminase levels, stomatitis, anemia, fever, mucositis, flu-like symptoms, and rash have been reported.
- Conditions
- Malignant Glioma, Glioblastoma, Gliosarcoma
- Being tested
- Bevacizumab, Temozolomide, Radiation Therapy (XRT), Topotecan
- Keywords
- malignant glioma, glioblastoma, gliosarcoma, Avastin, bevacizumab, Topotecan, Hycamtin, Temozolomide, Temodar, Pro00019960, Vredenburgh, Duke, Desjardins
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BevacizumabDrug
Also called Avastin
Bevacizumab (Avastin) at 10 mg/kg every other week during standard radiation therapy (XRT). Following XRT, bevacizumab will remain at 10 mg/kg every other week.
TemozolomideDrug
Also called Temodar
Daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation therapy (XRT). Following XRT, temozolomide will be dosed at 150 mg/m2 daily the first 5 days of each 28-day cycle.
Radiation Therapy (XRT)Radiation
Standard radiation therapy for approximately 6.5 weeks
TopotecanDrug
Also called Hycamtin
Following standard radiation therapy, patients will receive topotecan on days 2 through 6 of each 28-day cycle at a dose of 1.5 mg/m2 for patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs) and 2.0 mg/m2 for patients taking EIAEDs.
| Study group | Role | What they receive |
|---|---|---|
| Bevacizumab, XRT, Temozolomide, Topotecan | Experimental | Patients are treated with standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation. Following completion of radiation therapy, patients have a MRI and, if there is no evidence of disease progression, patients receive 12 cycles of Avastin, temozolomide, and topotecan. Beginning a minimum of 14 days after the last radiation treatment, the Avastin is dosed at 10 mg/kg every other week; temozolomide is given at 150 mg/m2 daily the first 5 days in combination with topotecan on days 2 through 6 at 1.5 mg/ m2 for patient not taking EIAEDs and 2.0 mg/ m2 for patients taking EIAEDs on days 2-6 of each 28-day. Receives: Drug: Bevacizumab; Drug: Temozolomide; Radiation: Radiation Therapy (XRT); Drug: Topotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
6-month Progression-free Survival
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 according to the Macdonald criteria, or to death due to any cause.
Measured: 6 months
Secondary outcomes (5)
One and Two Year Overall Survival
Time in months 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.
Measured: One year and two years
Median Overall Survival
OS was defined as time in months 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: 27 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: 27 months
Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity
Number of times a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity was experienced
Measured: 27 months
Median Progression-free Survival
PFS was defined as 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. 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: 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2009 (estimated)
- Study start30 Dec 2009
- Primary completionJul 2012
- Study completion2 Nov 2021
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 Malignant GliomaStudies 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
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01004874
- Sponsor's protocol ID
- Pro00019960
- Status last verified
- Mar 2022
- First submitted
- 28 Oct 2009
- Last updated
- 13 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2022. 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 Topotecan for Glioblastoma Multiformes and Gliosarcomas
- ClinicalTrials.gov ID
- NCT01004874
- Acronym / sponsor ID
- Pro00019960
- Conditions
- Malignant Glioma, Glioblastoma, Gliosarcoma
- Keywords
- malignant glioma, glioblastoma, gliosarcoma, Avastin, bevacizumab, Topotecan, Hycamtin, Temozolomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc., GlaxoSmithKline
- Study start
- 30 Dec 2009 (actual)
- Primary completion
- Jul 2012 (actual)
- Study completion
- 2 Nov 2021 (actual)
- First posted
- 30 Oct 2009 (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.
This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.
Detailed description
The primary objective of this study is to use 6-month progression-free survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objectives are to determine the overall survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan and to describe the toxicity of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan.
The study will have survival and toxicity endpoints. Patients will be treated with standard radiation therapy and daily temozolomide for 6 and a half weeks of radiation. Avastin will be administered every other week beginning a minimum of 28 days after the last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of radiation therapy, patients will have a MRI and if there is no evidence of disease progression, patients will receive 12 cycles of Avastin, temozolomide, and topotecan (beginning a minimum of 14 days after the last radiation treatment). Subjects will be identified by the investigator as those patients who have newly diagnosed grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma), and be within 6 weeks of the last major surgical procedure, craniotomy, open biopsy, or stereotactic biopsy.
Fifty (50) patients will initially be accrued to the study and the overall efficacy of the treatment regimen assessed. Analyses will be conducted within subgroups defined by methylation status.
Early side effects of radiation that may start during radiation include hair loss, scalp redness, inflammation of the ear canals, and fatigue. There is a small chance of long-term effects from radiation, occurring after months or years after completion. These may include worsening of mental function, hearing, vision, strength and coordination. In initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. Temozolomide has been well tolerated by both adults and children with the most common toxicity being mild myelosuppression. Other, less likely, potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash, burning sensation of skin, esophagitis, pain, diarrhea, lethargy, and hepatotoxicity. With topotecan, reversible myelosuppression with leukopenia and thrombocytopenia is dose limiting. Nausea and vomiting, as well as diarrhea and alopecia, are frequent. Moderate fatigue, transient elevation of hepatic transaminase levels, stomatitis, anemia, fever, mucositis, flu-like symptoms, and rash have been reported.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevacizumab, XRT, Temozolomide, Topotecan | Experimental | Drug: Bevacizumab, Drug: Temozolomide, Radiation: Radiation Therapy (XRT), Drug: TopotecanPatients are treated with standard radiation therapy and daily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation. Following completion of radiation therapy, patients have a MRI and, if there is no evidence of disease progression, patients receive 12 cycles of Avastin, temozolomide, and topotecan. Beginning a minimum of 14 days after the last radiation treatment, the Avastin is dosed at 10 mg/kg every other week; temozolomide is given at 150 mg/m2 daily the first 5 days in combination with topotecan on days 2 through 6 at 1.5 mg/ m2 for patient not taking EIAEDs and 2.0 mg/ m2 for patients taking EIAEDs on days 2-6 of each 28-day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma (glioblastoma multiforme or gliosarcoma). Patients have to be within 6 weeks of the last major surgical procedure.
- Age > or = to 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 > or = to 60%.
Key exclusion criteria (21 listed)
- Pregnancy or breast feeding.
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids.
- Active infection requiring IV antibiotics.
- Prior treatment with radiotherapy or chemotherapy for a brain tumor, irrespective of the grade of the tumor.
- Evidence of > grade 1 central nervous system (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 |
|---|---|---|
| BevacizumabAlso: AvastinBevacizumab (Avastin) at 10 mg/kg every other week during standard radiation therapy (XRT). Following XRT, bevacizumab will remain at 10 mg/kg every other week. | Drug | Bevacizumab, XRT, Temozolomide, Topotecan |
| TemozolomideAlso: TemodarDaily temozolomide at 75 mg/ m2 daily for 6.5 weeks of radiation therapy (XRT). Following XRT, temozolomide will be dosed at 150 mg/m2 daily the first 5 days of each 28-day cycle. | Drug | Bevacizumab, XRT, Temozolomide, Topotecan |
| Radiation Therapy (XRT)Standard radiation therapy for approximately 6.5 weeks | Radiation | Bevacizumab, XRT, Temozolomide, Topotecan |
| TopotecanAlso: HycamtinFollowing standard radiation therapy, patients will receive topotecan on days 2 through 6 of each 28-day cycle at a dose of 1.5 mg/m2 for patients not taking enzyme-inducing anti-epileptic drugs (EIAEDs) and 2.0 mg/m2 for patients taking EIAEDs. | Drug | Bevacizumab, XRT, Temozolomide, Topotecan |
Primary outcome
6-month Progression-free Survival
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 according to the Macdonald criteria, or to death due to any cause.
5 secondary outcomes
One and Two Year Overall Survival
Time frame: One year and two years
Median Overall Survival
Time frame: 27 months
Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage
Time frame: 27 months
Number of Patients Experiencing a Greater Than or Equal to Grade 4 Hematologic or a Greater Than or Equal to Grade 3 Non-hematologic Toxicity
Time frame: 27 months
Median Progression-free Survival
Time frame: 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- The Preston Robert Tisch Brain Tumor CenterLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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 University
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, Temozolomide and Radiation Therapy (XRT) in people with Malignant Glioma and Glioblastoma, 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 9 inclusion and 21 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 13 Apr 2022. 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?
6-month Progression-free Survival (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 13 Apr 2022.