Malignant GliomaPhase 2BBPNCT01740258
Bevacizumab Beyond Progression (BBP)
A Phase 2 study testing Radiation Therapy, Temozolomide and Bevacizumab in people with Malignant Glioma and Grade 4 Malignant Glioma, run by Duke University at 1 site in United States.
Trial summary
Studies which have separately studied bevacizumab for recurrent gliomas and bevacizumab for newly-diagnosed glioma have shown good results and the regimens have been well-tolerated by patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma, Grade 4 Malignant Glioma, Glioblastoma
- What is being tested?
- Radiation Therapy, Temozolomide and Bevacizumab
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2013to 14 Nov 2019
- 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 with histologically confirmed WHO Grade IV primary malignant glioma (glioblastoma or gliosarcoma);
- Patients ≥ 18 years of age;
- An interval of at least 2 weeks, but not ≥ 8 weeks between prior surgical procedure and initiation of treatment;
- Karnofsky Performance Status (KPS) ≥ 60%
- Laboratory Values:
- Platelet Count ≥ 125,000 cells/µL
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- Absolute neutrophil count (ANC) ≥ 1,500 cells/µL
- Adequate renal function indicated by all of the following:
- Serum creatinine ≤ 1.25 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 50 ml/min
- Urine dipstick for proteinuria < 2+ unless a 24-hour urine protein < 1 g of protein is demonstrated
- internationalized normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 x upper limit of normal (ULN) within 7 days prior to first study treatment for patients not receiving anti-coagulation. The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least two weeks prior to the first study treatment.
- Patients will sign an Institutional Review Board-approved informed consent form.
- Female patients must not be pregnant or breast-feeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intra-uterine device [Intrauterine Device (IUD); only hormonal], sexual abstinence or vasectomized partner) during the trial and for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 7 days prior to first study treatment.
- Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, Intrauterine Device (IUDs) [only hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of > 6 months following the last administration of trial drugs.
Who cannot join
- Any prior treatment for any grade glioma, including, but not limited to gliadel wafers, immunotherapy (including vaccine therapy), radiation therapy or chemotherapy, irrespective of grade of the tumor (NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.);
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
- Active infection requiring intravenous antibiotics;
- Prior or current treatment with bevacizumab or other anti-angiogenic treatment (i.e. anti-vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) therapies or tyrosine kinase inhibitors) for any condition;
- Treatment with any other investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first study treatment;
- Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin;
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- Evidence of > Grade 1 central nervous system (CNS) hemorrhage on post-operative MRI scan, unless repeat MRI or CT performed prior to initiating bevacizumab shows stable grade 1 or resolving (< grade 1) CNS hemorrhage.
- Bevacizumab-Specific Exclusion Criteria:
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) within 28 days of first study treatment;
- Prior history of hypertensive crisis, hypertensive encephalopathy, reverse posterior leukoencephalopathy syndrome (RPLS);
- Prior history of gastrointestinal perforation or abscess;
- Clinically significant (i.e. active) cardiovascular disease, for example cerebrovascular accidents ≤ 6 months prior to study enrollment, myocardial infarction ≤ 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF), or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment;
- History or evidence upon physical/neurological examination of central nervous system disease (e.g. seizures) unrelated to cancer unless adequately controlled by medication or potentially interfering with protocol treatment;
- Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months prior to start of study treatment. Any previous venous thromboembolism > NCI common toxicity criteria adverse event (CTCAE) Grade 3;
- History of pulmonary hemorrhage/hemoptysis ≥ grade 2 (defined as ≥ 2.5 mL bright red blood per episode) within 1 month of first study treatment;
- History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation);
- Current or recent (within 10 days of study enrollment) use of aspirin (>325 mg/day), clopidogrel (>75 mg/day) or equivalent. Prophylactic use of anticoagulants is allowed;
- Surgical procedure (including open biopsy, surgical resection, wound revision, or any other major surgery involving entry into a body cavity) or significant traumatic injury within 28 days prior to first study treatment, or anticipation of need for major surgical procedure during the course of the study;
- Minor surgical procedure, e.g. stereotactic biopsy, within 7 days of first study treatment; placement of a vascular access device, within 2 days of first study treatment;
- History of intracranial abscess within 6 months prior to first study treatment;
- History of active gastrointestinal bleeding within 6 months prior to first study treatment;
- Serious, non-healing wound, active ulcer, or untreated bone fracture;
- Known hypersensitivity to any component of bevacizumab or any of the study drugs;
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Trial of Bevacizumab, Radiation Therapy and Temodar Followed by Bevacizumab and Temodar With Continuation of Bevacizumab Beyond Progression (BBP-Bevacizumab Beyond Progression)
Studies which have separately studied bevacizumab for recurrent gliomas and bevacizumab for newly-diagnosed glioma have shown good results and the regimens have been well-tolerated by patients. This study seeks to investigate the use of bevacizumab with the standard therapy (radiation therapy and temozolomide) in newly diagnosed patients, followed by bevacizumab and temozolomide with the continuation of bevacizumab following progression. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis.
Read the detailed description
Given the possible synergism with irinotecan and bevacizumab for colorectal carcinomas, the combination has been studied in gliomas. In a study of 21 patients, the combination of irinotecan and bevacizumab produced a 43% response rate, with acceptable toxicity. The response rate is significantly higher than irinotecan alone and any other therapy for recurrent glioma. There were two serious adverse events, one intracranial hemorrhage and one bowel perforation. At the Duke Brain Tumor Center, the investigators have treated over 1000 glioblastoma patients with a bevacizumab-containing regimen, and there is marked clinical benefit and acceptable toxicity. Our initial study looking at the combination of bevacizumab and irinotecan for patients with recurrent glioblastoma published in 2007 found impressive response rates and survival and corroborated the earlier experience of Starks-Vance.
The investigators completed a study for newly diagnosed glioblastoma that utilized bevacizumab, radiation therapy and temozolomide followed by 6 months of bevacizumab, irinotecan and temozolomide. In addition, the group at University of California at Los Angeles published a study with bevacizumab, radiation therapy and temozolomide followed by 12 months of bevacizumab and temozolomide for newly diagnosed glioblastoma. These two phase II studies reported acceptable toxicity and a suggestion of improved survival compared to historical controls, and led to two large phase III randomized, placebo controlled studies of the addition of bevacizumab for newly diagnosed glioblastoma patients. The current proposal builds on the encouraging results of the addition of bevacizumab to the standard therapy for newly diagnosed glioblastoma patients. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis. In addition, a retrospective analysis of data collected at our center from patients with recurrent disease suggests that continuation of bevacizumab at the time of progression may improve overall survival in comparison with cessation of bevacizumab.
- Conditions
- Malignant Glioma, Grade 4 Malignant Glioma, Glioblastoma, Gliosarcoma
- Being tested
- Radiation Therapy, Temozolomide, Bevacizumab
- Keywords
- malignant glioma, Grade 4 malignant glioma, glioblastoma, gliosarcoma, adult brain tumor
- Medical subject headings
- Glioma, Glioblastoma, Gliosarcoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Radiation TherapyRadiation
Also called XRT
TemozolomideDrug
Also called temo, temodar
BevacizumabDrug
Also called Avastin
| Study group | Role | What they receive |
|---|---|---|
| Bevaczimab, Radiation Therapy, Temozolomide | Experimental | In Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks.
If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle.
If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks.
If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. Receives: Radiation: Radiation Therapy; Drug: Temozolomide; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
To assess the effect on overall survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of first diagnosis of grade IV malignant glioma.
Measured: 5 Years
Secondary outcomes (2)
Toxicity: Percentage of Subjects With Unacceptable Toxicities
The occurrence of ≥ grade 2 CNS (central nervous system) hemorrhage or grade 4 or 5 non-hematologic toxicity is defined as being unacceptable. "Unacceptable" toxicity rates of 5% or less are considered desirable, while rates of 20% or greater are considered as undesirable.
Measured: 5 Years
Progression-free Survival (PFS)
To assess the effect on progression-free survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of initiation of treatment to the first occurrence of progression, or death
Measured: 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2012 (estimated)
- Study startJan 2013
- Primary completion14 Nov 2019
- Study completion14 Nov 2019
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
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Annick Desjardins, MD, FRCPC, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01740258
- Sponsor's protocol ID
- Pro00038098
- Acronym
- BBP
- Status last verified
- Jan 2021
- First submitted
- 30 Nov 2012
- Last updated
- 26 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Bevacizumab, Radiation Therapy and Temodar Followed by Bevacizumab and Temodar With Continuation of Bevacizumab Beyond Progression (BBP-Bevacizumab Beyond Progression)
- ClinicalTrials.gov ID
- NCT01740258
- Acronym / sponsor ID
- BBP / Pro00038098
- Conditions
- Malignant Glioma, Grade 4 Malignant Glioma, Glioblastoma, Gliosarcoma
- Keywords
- malignant glioma, Grade 4 malignant glioma, glioblastoma, gliosarcoma, adult brain tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jan 2013 (actual)
- Primary completion
- 14 Nov 2019 (actual)
- Study completion
- 14 Nov 2019 (actual)
- First posted
- 4 Dec 2012 (estimated)
- Results
- Posted 2 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Studies which have separately studied bevacizumab for recurrent gliomas and bevacizumab for newly-diagnosed glioma have shown good results and the regimens have been well-tolerated by patients. This study seeks to investigate the use of bevacizumab with the standard therapy (radiation therapy and temozolomide) in newly diagnosed patients, followed by bevacizumab and temozolomide with the continuation of bevacizumab following progression. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis.
Detailed description
Given the possible synergism with irinotecan and bevacizumab for colorectal carcinomas, the combination has been studied in gliomas. In a study of 21 patients, the combination of irinotecan and bevacizumab produced a 43% response rate, with acceptable toxicity. The response rate is significantly higher than irinotecan alone and any other therapy for recurrent glioma. There were two serious adverse events, one intracranial hemorrhage and one bowel perforation. At the Duke Brain Tumor Center, the investigators have treated over 1000 glioblastoma patients with a bevacizumab-containing regimen, and there is marked clinical benefit and acceptable toxicity. Our initial study looking at the combination of bevacizumab and irinotecan for patients with recurrent glioblastoma published in 2007 found impressive response rates and survival and corroborated the earlier experience of Starks-Vance.
The investigators completed a study for newly diagnosed glioblastoma that utilized bevacizumab, radiation therapy and temozolomide followed by 6 months of bevacizumab, irinotecan and temozolomide. In addition, the group at University of California at Los Angeles published a study with bevacizumab, radiation therapy and temozolomide followed by 12 months of bevacizumab and temozolomide for newly diagnosed glioblastoma. These two phase II studies reported acceptable toxicity and a suggestion of improved survival compared to historical controls, and led to two large phase III randomized, placebo controlled studies of the addition of bevacizumab for newly diagnosed glioblastoma patients. The current proposal builds on the encouraging results of the addition of bevacizumab to the standard therapy for newly diagnosed glioblastoma patients. Two critical questions remain- the role of bevacizumab maintenance and bevacizumab at the time of progression in a patient previously treated with bevacizumab at the time of initial diagnosis. In addition, a retrospective analysis of data collected at our center from patients with recurrent disease suggests that continuation of bevacizumab at the time of progression may improve overall survival in comparison with cessation of bevacizumab.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bevaczimab, Radiation Therapy, Temozolomide | Experimental | Radiation: Radiation Therapy, Drug: Temozolomide, Drug: BevacizumabIn Part A, newly-diagnosed patients with Grade 4 malignant gliomas will receive standard radiation therapy, daily Temodar 75mg/M for 6-8 weeks. Bevacizumab will be given concurrently with radiation therapy and Temodar, 10 mg/kg every two weeks. If they are stable at the end of Part A, they will continue to Part B. In Part B patients will receive up to 12 cycles of bevacizumab and Temodar. Bevacizumab will be given on Days 1 and 15 of a 28-day cycle. Temodar will be 200 mg/meter squared daily for 5 days (days 1-5) of each cycle. If they have not progressed, patients will start Part C. In Part C, patients will receive bevacizumab 10mg/kg approximately every 2 weeks or 15 mg/kg approximately every 3 weeks. If patients progress during Part B or C, they will start Part D. In Part D, patients will receive bevacizumab-based therapy containing bevacizumab in combination with a chemotherapy and/or biologic agent, as determined by the Duke treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients with histologically confirmed WHO Grade IV primary malignant glioma (glioblastoma or gliosarcoma);
- Patients ≥ 18 years of age;
- An interval of at least 2 weeks, but not ≥ 8 weeks between prior surgical procedure and initiation of treatment;
- Karnofsky Performance Status (KPS) ≥ 60%
- Laboratory Values:
Key exclusion criteria (23 listed)
- Any prior treatment for any grade glioma, including, but not limited to gliadel wafers, immunotherapy (including vaccine therapy), radiation therapy or chemotherapy, irrespective of grade of the tumor (NOTE: 5-aminolevulinic acid (ALA)-mediated photodynamic therapy administered prior to surgery to aid in optimal surgical resection is not considered a chemotherapy agent.);
- Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids;
- Active infection requiring intravenous antibiotics;
- Prior or current treatment with bevacizumab or other anti-angiogenic treatment (i.e. anti-vascular endothelial growth factor (VEGF) or vascular endothelial growth factor receptor (VEGFR) therapies or tyrosine kinase inhibitors) for any condition;
- Treatment with any other investigational agent within 28 days or 2 investigational agent half-lives (whichever is longer) prior to first 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: XRT | Radiation | Bevaczimab, Radiation Therapy, Temozolomide |
| TemozolomideAlso: temo, temodar | Drug | Bevaczimab, Radiation Therapy, Temozolomide |
| BevacizumabAlso: Avastin | Drug | Bevaczimab, Radiation Therapy, Temozolomide |
Primary outcome
Overall Survival
Time frame: 5 Years
To assess the effect on overall survival of continuing bevacizumab treatment after disease progression in patients treated with bevacizumab from the time of first diagnosis of grade IV malignant glioma.
2 secondary outcomes
Toxicity: Percentage of Subjects With Unacceptable Toxicities
Time frame: 5 Years
Progression-free Survival (PFS)
Time frame: 5 Years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Preston Robert Tisch Brain Tumor Center at DukeLink provided by the sponsor.
- Duke Cancer InstituteLink provided by the sponsor.
- Duke Cancer Center - Patient CareLink 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 Radiation Therapy, Temozolomide and Bevacizumab in people with Malignant Glioma and Grade 4 Malignant Glioma, 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 14 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 26 Jan 2021. 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 2 Dec 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?
Overall Survival (time frame: 5 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 26 Jan 2021.