Newly Diagnosed High-Grade GliomasEarly Phase 1NCT00890786
A Study of Bevacizumab Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
A Early Phase 1 study testing Temozolomide, Bevacizumab and Irinotecan in people with Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Glioma, run by Children's Hospital Medical Center, Cincinnati at 2 sites in United States.
Trial summary
The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy. Read more about this study
- Who is it for?
- Ages 3 to 30 years
- Conditions the study is for
- Newly Diagnosed High-Grade Gliomas, Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Temozolomide, Bevacizumab and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 2 sitesUnited States
- Study dates
- May 2009to Dec 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 3 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must be ≥ 3 years of age and ≤ 30 years of age at the time of study entry.
- Diagnosis:
- High-grade glioma;Patients must have had histologically verified anaplastic astrocytoma, glioblastoma multiforme or gliosarcoma.Patients with primary spinal cord tumors are eligible.
- Diffuse intrinsic pontine glioma (DIPG) are eligible.
- Performance Level: Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Prior Therapy: no prior anticancer therapy.
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- Concomitant Medications: The use of steroids is permissible.
- Organ Function Requirements All patients must have adequate organ function as defined below.
- Adequate Bone Marrow Function
- Adequate Renal Function
- Adequate Liver Function
- Adequate Blood Clotting Defined As: INR, Fibrinogen, and PTT < Grade 2
- Central nervous system function. Patients with seizures may be enrolled if the seizures are well-controlled with non-enzyme inducing anticonvulsants.
- Informed Consent. Patients and/or parents/legal guardians must have signed an informed consent.
Who cannot join
- Patients with metastatic disease (i.e. M+ disease, or disease anywhere other than primary site).
- Patients with evidence of a new intracranial hemorrhage that is larger than a punctate size on baseline MRI scan.
- Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.
- Pregnant or breast feeding women will not be entered on this study.
- Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
- Infection: Patients who require IV antibiotics at time of enrollment, or who are currently receiving treatment for Clostridium difficile infection are excluded.
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- Thrombosis: Patients must not have been previously diagnosed with a deep venous or arterial thrombosis (including pulmonary embolism), and must not have a known thrombophilic condition.
- Serious or Non-Healing Wounds
- Surgical Procedures: Patients who have had major surgery should not receive the first dose of bevacizumab until 28 days after major surgery.
- Patients with uncontrolled systemic hypertension.
- Proteinuria with a urine protein (albumin)/creatinine ratio of ≥1.0.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60614
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy.
Read the detailed description
Novel therapies are needed to improve the outcome of these children. Recent studies have demonstrated very promising results of treatment with bevacizumab/irinotecan in patients with recurrent high grade gliomas. Based on these promising results, and the tolerability of the irinotecan and bevacizumab in children with recurrent CNS malignancies both anecdotally and in a study conducted by the Pediatric Brain Tumor Consortium, we have designed a novel study incorporating concurrent radiation therapy with bevacizumab ± temozolomide followed by bevacizumab, irinotecan ±temozolomide in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.
- Being tested
- Temozolomide, Bevacizumab, Irinotecan
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar
High Grade Glioma Temozolomide during radiotherapy: 90mg/m2/day PO daily (for patients ≤ 18 years of age); 75mg/m2/day PO daily (for patients ≥ 19 years of age); must begin by Day 5 of radiotherapy for a total of 42 days consecutively.
High Grade Glioma Temozolomide during maintenance chemotherapy: 150mg/m2/day PO on Days 1-5.
BevacizumabDrug
Also called Avastin
High Grade Glioma Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Day 22 (± 2 days)and Day 36 (± 2 days) of radiotherapy.
High Grade Glioma Bevacizumab during maintenance chemotherapy:10 mg/kg as a 90 minute infusion on Day 1 (+ 2 days)and Day 15 (± 2 days) of each course.
Diffuse Intrinsic Pontine Gliomas Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Days 1 (+ 2 days),15, 29, and 43(±2 days for all 3 doses) of radiotherapy.
Diffuse Intrinsic Pontine Gliomas Bevacizumab during maintenance chemotherapy: 10 mg/kg as a 90 minute infusion on Day 1 (+2 days)and 15 (±2 days).
IrinotecanDrug
Also called Camptosar
High Grade Glioma Irinotecan during maintenance chemotherapy:125 mg/m2/day IV over 90 minutes on Days 1 (+ 2 days)and 15 (±2 days) of each course, given no sooner than one hour after temozolomide on Day 1.
Diffuse Intrinsic Pontine Gliomas Irinotecan maintenance chemotherapy: 125 mg/m2/day IV on Day 1 (+2 days)and Day 15 (±2 days).
| Study group | Role | What they receive |
|---|---|---|
| HGG | Experimental | Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section. Receives: Drug: Temozolomide; Drug: Bevacizumab; Drug: Irinotecan |
| DIPG | Experimental | Temozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section. Receives: Drug: Temozolomide; Drug: Bevacizumab; Drug: Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the toxicities and feasibility of the proposed treatment regimen in patients with high-grade glioma and diffuse intrinsic brainstem glioma
Measured: 2-3 years
Secondary outcomes (10)
To determine 1-year EFS, median PFS and median OS in newly diagnosed patients with high-grade glioma treated with radiotherapy and concurrent temozolomide, bevacizumab followed by bevacizumab, irinotecan and temozolomide for 12 courses
Measured: 2-3 years
To determine the 1-year EFS, median PFS and median OS in newly diagnosed patients with diffuse intrinsic brainstem glioma treated with radiotherapy and concurrent bevacizumab followed by bevacizumab and irinotecan for 12 courses
Measured: 2-3 years
To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
Measured: 2-3 years
To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy
Measured: 2-3 years
To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
Measured: 2-3 years
To correlate the results of the biology studies in serum or tumor with PFS
Measured: 2-3 years
To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
Measured: 2-3 years
To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
Measured: 2-3 years
To assess the health-related quality of life of patients by parent report, and when possible, patient report at key points in therapy
Measured: 2-3 years
To assess functional abilities and level of independence of patients during and following treatment
Measured: 2-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionOct 2014
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Newly Diagnosed High-Grade GliomasStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Sponsor
- Investigators
- Maryam Fouladi, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00890786
- Sponsor's protocol ID
- HGG
- Status last verified
- May 2018
- First submitted
- 29 Apr 2009
- Last updated
- 2 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Bevacizumab-Based Therapy in Patients With Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Gliomas
- ClinicalTrials.gov ID
- NCT00890786
- Acronym / sponsor ID
- HGG
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- May 2009
- Primary completion
- Oct 2014 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 30 Apr 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The outcome for children with high-grade gliomas and diffuse intrinsic brainstem gliomas remains poor despite the use of multi-modal therapy with surgery, radiation therapy and chemotherapy.
Detailed description
Novel therapies are needed to improve the outcome of these children. Recent studies have demonstrated very promising results of treatment with bevacizumab/irinotecan in patients with recurrent high grade gliomas. Based on these promising results, and the tolerability of the irinotecan and bevacizumab in children with recurrent CNS malignancies both anecdotally and in a study conducted by the Pediatric Brain Tumor Consortium, we have designed a novel study incorporating concurrent radiation therapy with bevacizumab ± temozolomide followed by bevacizumab, irinotecan ±temozolomide in patients with newly diagnosed high-grade gliomas and diffuse intrinsic pontine gliomas.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HGG | Experimental | Drug: Temozolomide, Drug: Bevacizumab, Drug: IrinotecanTemozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the intervention section. |
| DIPG | Experimental | Drug: Temozolomide, Drug: Bevacizumab, Drug: IrinotecanTemozolomide, Bevacizumab, and Irinotecan according to the treatment schedule in the interventions section. |
Who may qualify
- Ages
- 3 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Patients must be ≥ 3 years of age and ≤ 30 years of age at the time of study entry.
- Diagnosis:
- Performance Level: Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Prior Therapy: no prior anticancer therapy.
- Concomitant Medications: The use of steroids is permissible.
Key exclusion criteria (11 listed)
- Patients with metastatic disease (i.e. M+ disease, or disease anywhere other than primary site).
- Patients with evidence of a new intracranial hemorrhage that is larger than a punctate size on baseline MRI scan.
- Allergies: Patients with a history of allergic reaction to Chinese hamster ovary cell products, or other recombinant human antibodies.
- Pregnant or breast feeding women will not be entered on this study.
- Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
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 |
|---|---|---|
| TemozolomideAlso: TemodarHigh Grade Glioma Temozolomide during radiotherapy: 90mg/m2/day PO daily (for patients ≤ 18 years of age); 75mg/m2/day PO daily (for patients ≥ 19 years of age); must begin by Day 5 of radiotherapy for a total of 42 days consecutively. High Grade Glioma Temozolomide during maintenance chemotherapy: 150mg/m2/day PO on Days 1-5. | Drug | DIPG, HGG |
| BevacizumabAlso: AvastinHigh Grade Glioma Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Day 22 (± 2 days)and Day 36 (± 2 days) of radiotherapy. High Grade Glioma Bevacizumab during maintenance chemotherapy:10 mg/kg as a 90 minute infusion on Day 1 (+ 2 days)and Day 15 (± 2 days) of each course. Diffuse Intrinsic Pontine Gliomas Bevacizumab during radiotherapy: 10 mg/kg as a 90 minute infusion on Days 1 (+ 2 days),15, 29, and 43(±2 days for all 3 doses) of radiotherapy. Diffuse Intrinsic Pontine Gliomas Bevacizumab during maintenance chemotherapy: 10 mg/kg as a 90 minute infusion on Day 1 (+2 days)and 15 (±2 days). | Drug | DIPG, HGG |
| IrinotecanAlso: CamptosarHigh Grade Glioma Irinotecan during maintenance chemotherapy:125 mg/m2/day IV over 90 minutes on Days 1 (+ 2 days)and 15 (±2 days) of each course, given no sooner than one hour after temozolomide on Day 1. Diffuse Intrinsic Pontine Gliomas Irinotecan maintenance chemotherapy: 125 mg/m2/day IV on Day 1 (+2 days)and Day 15 (±2 days). | Drug | DIPG, HGG |
Primary outcome
To determine the toxicities and feasibility of the proposed treatment regimen in patients with high-grade glioma and diffuse intrinsic brainstem glioma
Time frame: 2-3 years
10 secondary outcomes
To determine 1-year EFS, median PFS and median OS in newly diagnosed patients with high-grade glioma treated with radiotherapy and concurrent temozolomide, bevacizumab followed by bevacizumab, irinotecan and temozolomide for 12 courses
Time frame: 2-3 years
To determine the 1-year EFS, median PFS and median OS in newly diagnosed patients with diffuse intrinsic brainstem glioma treated with radiotherapy and concurrent bevacizumab followed by bevacizumab and irinotecan for 12 courses
Time frame: 2-3 years
To estimate blood levels of VEGF in circulating endothelial cells in patients at different time points
Time frame: 2-3 years
To document changes in MR perfusion and diffusion within 24-48 hours after the 2nd dose of bevacizumab during radiotherapy
Time frame: 2-3 years
To correlate functional changes in tumor with responses to treatment using MR diffusion/perfusion imaging
Time frame: 2-3 years
To correlate the results of the biology studies in serum or tumor with PFS
Time frame: 2-3 years
To conduct gene expression profiling, CGH and SNP arrays in patients with high-grade gliomas
Time frame: 2-3 years
To assess telomerase activity, hTert expression, and telomere length in patients with high-grade gliomas
Time frame: 2-3 years
To assess the health-related quality of life of patients by parent report, and when possible, patient report at key points in therapy
Time frame: 2-3 years
To assess functional abilities and level of independence of patients during and following treatment
Time frame: 2-3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2018.
- 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.
Maryam Fouladi, MD principal investigator
Children's Hospital Medical Center, Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Temozolomide, Bevacizumab and Irinotecan in people with Newly Diagnosed High-Grade Gliomas and Diffuse Intrinsic Pontine Glioma, run by Children's Hospital Medical Center, Cincinnati at 2 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 14 inclusion and 11 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 2 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the toxicities and feasibility of the proposed treatment regimen in patients with high-grade glioma and diffuse intrinsic brainstem glioma (time frame: 2-3 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 2 May 2018.