Glioblastoma MultiformePhase 2NCT00805961
RT, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in First-line Treatment of GBM
A Phase 2 study testing Radiation therapy, Temozolomide and Bevacizumab in people with Glioblastoma Multiforme, run by SCRI Development Innovations, LLC at 13 sites in United States.
Trial summary
In this phase II trial the investigators plan to incorporate two targeted agents, bevacizumab and everolimus, into the first-line multimodality therapy of glioblastoma. In the first portion of the treatment, bevacizumab will be added to standard concurrent radiation therapy plus temozolomide. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma Multiforme
- What is being tested?
- Radiation therapy, Temozolomide and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 13 sitesUnited States
- Study dates
- Jan 2009to 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
- Age >=18 years.
- Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment with radiotherapy or systemic therapy. Local therapy with a Gliadel wafer placed at the time of surgical debulking is permitted.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate bone marrow function
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- Adequate liver function:
- Serum creatinine <=1.5 x institutional ULN.
- Ability to swallow whole pills.
- Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to start of treatment. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment and for 6 months after the last study treatment. Hormonal contraceptives are not acceptable as a sole method of contraception. Female patients must not breast feed.
- INR <1.3 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of everolimus and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Fasting serum cholesterol <=300 mg/dL OR <=7.75 mmol/L AND fasting triglycerides <= 2.5 x institutional ULN.
Who cannot join
- New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix B) or symptomatic congestive heart failure.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg).
- History of myocardial infarction or unstable angina within 6 months prior to beginning study treatment.
- History of stroke or transient ischemic attack within 6 months prior to beginning study treatment.
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to beginning study treatment.
- Prior history of hypertensive crisis or hypertensive encephalopathy.
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- History of hemoptysis (>=1/2 teaspoon of bright red blood per episode) within 1 month prior to beginning study treatment.
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation).
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1.
- Serious, non-healing wound, active ulcer, or untreated bone fracture.
- Proteinuria as demonstrated by urine dipstick for proteinuria >=2+. For patients with >=2+ proteinuria on dipstick urinalysis, a urine protein: creatinine (UPC) ratio will be determined or a 24-hour urine collection will be done. Patients with a UPC ratio <1 or a 24-hour urine protein <1 gram are eligible.
- Minor surgical procedures (excluding placement of a vascular access device), fine-needle aspirations, or core biopsies within 7 days prior to starting treatment.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting protocol treatment or anticipation of need for major surgical procedure during the course of study treatment. Patients who have not recovered from the side effects of any major surgery are not eligible.
- Treatment with any investigational agents within 4 weeks of study entry.
- Chronic, systemic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled steroids are allowed.
- Other malignancies within the past 3 years except for adequately treated carcinoma in situ of the cervix or basal cell or superficial squamous (skin cell) carcinomas.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Center for Cancer and Blood Disorders
Bethesda, Maryland, 20817
St. Louis Cancer Care
Chesterfield, Missouri, 63017
South Carolina Oncology Associates, PA
Columbia, South Carolina, 29210
Florida Cancer Specialists
Fort Myers, Florida, 33901
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Grand Rapids Clinical Oncology Program
Grand Rapids, Michigan, 49503
Clearview Cancer Institute
Huntsville, Alabama, 35805
Research Medical Center
Kansas City, Missouri, 64132
Consultants in Blood Disorders and Cancer
Louisville, Kentucky, 40207
Tennessee Oncology, PLLC
Nashville, Tennessee, 37023
Peninsula Cancer Institute
Newport News, Virginia, 23601
Methodist Cancer Center
Omaha, Nebraska, 68114
Virginia Cancer Institute
Richmond, Virginia, 23235
About this study
Official title: A Phase II Study of Concurrent Radiation Therapy, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in the First-line of Treatment of Patients With Glioblastoma Multiforme
In this phase II trial the investigators plan to incorporate two targeted agents, bevacizumab and everolimus, into the first-line multimodality therapy of glioblastoma. In the first portion of the treatment, bevacizumab will be added to standard concurrent radiation therapy plus temozolomide. After completing radiation therapy, patients will continue treatment with the combination of bevacizumab and everolimus.
Read the detailed description
Although this maintenance regimen departs from the standard treatment with single agent temozolomide, we feel this approach may add to the overall efficacy of treatment for the following reasons: 1) results with bevacizumab/everolimus in renal cell carcinoma suggest there is at least an additive efficacy when these drugs are used in combination; 2) the efficacy of single agent temozolomide following standard concurrent radiation therapy/temozolomide has not been proven, 3) the use of the three-drug maintenance program (i.e., bevacizumab/everolimus/temozolomide) would probably not be tolerated well on a chronic basis in this patient population; and 4) the bevacizumab/everolimus combination has potential advantages as a maintenance therapy, since it has been well tolerated for many months in patients with other malignancies.
- Conditions
- Glioblastoma Multiforme
- Being tested
- Radiation therapy, Temozolomide, Bevacizumab, Everolimus
- Keywords
- Glioblastoma Multiforme, Radiation Therapy, Temozolomide, Bevacizumab, Everolimus
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation therapyRadiation
Also called Combined Modality Treatment
Radiation therapy, 2.0 Gy daily, 5 days per week by single daily dose, to a total of 60 Gy over 6 weeks
TemozolomideDrug
Also called Combined Modality Treatment
Temozolomide 75mg/m2 by mouth daily, beginning day 1 of radiation therapy and continuing through the last day of radiation therapy
BevacizumabDrug
Also called Combined Modality Treatment
Bevacizumab 10mg/kg IV, every 2 weeks, beginning day 1 of radiation therapy
BevacizumabDrug
Also called Systemic Therapy
Bevacizumab 10mg/kg IV, every 2 weeks, beginning Week 11
EverolimusDrug
Also called Systemic Therapy
Everolimus 10mg by mouth daily, beginning Week 11
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Experimental | Combined Modality Treatment and Systemic Therapy
Combined Modality Therapy - Radiation Therapy: 2 Gy/fraction, single daily fractions Monday-Friday, to total of 60 Gy Temozolomide: 75 mg/m2 by mouth daily Bevacizumab: 10 mg/kg IV every 2 weeks (Weeks 1, 3, 5, and 7)
After the last dose of radiation, patients exhibiting an objective response, stable disease on MRI scan, or have stable/improved tumor-related symptoms will begin systemic therapy
Systemic Therapy - Bevacizumab: 10 mg/kg IV every 2 weeks Everolimus: 10 mg by mouth daily Receives: Radiation: Radiation therapy; Drug: Temozolomide; Drug: Bevacizumab; Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS)
Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Measured: 18 months
Secondary outcomes (3)
Number of Participants Experiencing Toxicity After This Novel Multimodality Regimen
The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here.
Measured: 18 months
Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen
Overall survival was defined as the interval from the first day of study treatment until the date of death.
Measured: 18 months
Objective Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen
Response to treatment was assessed by MRI using the MacDonald criteria based on the assessment of the MRI scan for measurable, evaluable, and new lesions. The objective response rate is defined as the proportion of patients with improvement and or decreased extent of lesions compared to baseline.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2008 (estimated)
- Study startJan 2009
- Primary completionOct 2009
- 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma MultiformeStudies of the same condition, open and under way.
- 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
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc., Novartis
- Responsible party
- Sponsor
- Investigators
- John D Hainsworth, M.D., Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00805961
- Sponsor's protocol ID
- SCRI CNS 10
- Status last verified
- Nov 2021
- First submitted
- 9 Dec 2008
- Last updated
- 8 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT, Spigel DR. Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 2012 Apr;10(4):240-6.
PubMed 22706484
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Concurrent Radiation Therapy, Temozolomide, and Bevacizumab Followed by Bevacizumab/Everolimus in the First-line of Treatment of Patients With Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT00805961
- Acronym / sponsor ID
- SCRI CNS 10
- Conditions
- Glioblastoma Multiforme
- Keywords
- Glioblastoma Multiforme, Radiation Therapy, Temozolomide, Bevacizumab, Everolimus
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Genentech, Inc., Novartis
- Study start
- Jan 2009
- Primary completion
- Oct 2009 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 10 Dec 2008 (estimated)
- Results
- Posted 21 Sep 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this phase II trial the investigators plan to incorporate two targeted agents, bevacizumab and everolimus, into the first-line multimodality therapy of glioblastoma. In the first portion of the treatment, bevacizumab will be added to standard concurrent radiation therapy plus temozolomide. After completing radiation therapy, patients will continue treatment with the combination of bevacizumab and everolimus.
Detailed description
Although this maintenance regimen departs from the standard treatment with single agent temozolomide, we feel this approach may add to the overall efficacy of treatment for the following reasons: 1) results with bevacizumab/everolimus in renal cell carcinoma suggest there is at least an additive efficacy when these drugs are used in combination; 2) the efficacy of single agent temozolomide following standard concurrent radiation therapy/temozolomide has not been proven, 3) the use of the three-drug maintenance program (i.e., bevacizumab/everolimus/temozolomide) would probably not be tolerated well on a chronic basis in this patient population; and 4) the bevacizumab/everolimus combination has potential advantages as a maintenance therapy, since it has been well tolerated for many months in patients with other malignancies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Experimental | Radiation: Radiation therapy, Drug: Temozolomide, Drug: Bevacizumab, Drug: EverolimusCombined Modality Treatment and Systemic Therapy Combined Modality Therapy - Radiation Therapy: 2 Gy/fraction, single daily fractions Monday-Friday, to total of 60 Gy Temozolomide: 75 mg/m2 by mouth daily Bevacizumab: 10 mg/kg IV every 2 weeks (Weeks 1, 3, 5, and 7) After the last dose of radiation, patients exhibiting an objective response, stable disease on MRI scan, or have stable/improved tumor-related symptoms will begin systemic therapy Systemic Therapy - Bevacizumab: 10 mg/kg IV every 2 weeks Everolimus: 10 mg by mouth daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age >=18 years.
- Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment with radiotherapy or systemic therapy. Local therapy with a Gliadel wafer placed at the time of surgical debulking is permitted.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (16 listed)
- New York Heart Association (NYHA) grade II or greater congestive heart failure (see Appendix B) or symptomatic congestive heart failure.
- Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg).
- History of myocardial infarction or unstable angina within 6 months prior to beginning study treatment.
- History of stroke or transient ischemic attack within 6 months prior to beginning study treatment.
- Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to beginning study treatment.
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 |
|---|---|---|
| Radiation therapyAlso: Combined Modality TreatmentRadiation therapy, 2.0 Gy daily, 5 days per week by single daily dose, to a total of 60 Gy over 6 weeks | Radiation | Intervention |
| TemozolomideAlso: Combined Modality TreatmentTemozolomide 75mg/m2 by mouth daily, beginning day 1 of radiation therapy and continuing through the last day of radiation therapy | Drug | Intervention |
| BevacizumabAlso: Combined Modality TreatmentBevacizumab 10mg/kg IV, every 2 weeks, beginning day 1 of radiation therapy | Drug | Intervention |
| BevacizumabAlso: Systemic TherapyBevacizumab 10mg/kg IV, every 2 weeks, beginning Week 11 | Drug | Intervention |
| EverolimusAlso: Systemic TherapyEverolimus 10mg by mouth daily, beginning Week 11 | Drug | Intervention |
Primary outcome
Progression-free Survival (PFS)
Time frame: 18 months
Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
3 secondary outcomes
Number of Participants Experiencing Toxicity After This Novel Multimodality Regimen
Time frame: 18 months
Overall Survival of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen
Time frame: 18 months
Objective Response Rate of Patients With Glioblastoma Multiforme Following Treatment With This Novel Multimodality Regimen
Time frame: 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22706484Hainsworth JD, Shih KC, Shepard GC, Tillinghast GW, Brinker BT, Spigel DR. Phase II study of concurrent radiation therapy, temozolomide, and bevacizumab followed by bevacizumab/everolimus as first-line treatment for patients with glioblastoma. Clin Adv Hematol Oncol. 2012 Apr;10(4):240-6.
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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.
John D Hainsworth, M.D. study chair
SCRI Development Innovations, LLC
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Radiation therapy, Temozolomide and Bevacizumab in people with Glioblastoma Multiforme, run by SCRI Development Innovations, LLC at 13 sites 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 16 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 8 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites 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 21 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?
Progression-free Survival (PFS) (time frame: 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00805961, which also lists 1 linked publication.
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 8 Dec 2021.