Low Grade GliomaPhase 2NCT02840409
Vinblastine +/- Bevacizumab in Children With Unresectable or Progressive Low Grade Glioma (LGG)
A Phase 2 study testing Vinblastine and Bevacizumab in people with Low Grade Glioma, run by The Hospital for Sick Children at 21 sites in 4 countries.
Trial summary
This is an open-label, randomized, multi-center, comparator Phase II trial looking at the addition of Bevacizumab to Vinblastine in chemotherapy naïve pediatric patients with progressive Low Grade Glioma aged 6 months to less than18 years of age at the time of initiation of therapy. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- Low Grade Glioma
- What is being tested?
- Vinblastine and Bevacizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 21 sitesin 4 countries
- Study dates
- 1 Aug 2016to Aug 2026
- Phase
- Phase 2
- 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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma (See Appendix I).
- All patients must submit tumour tissue (fresh tumour tissue is recommended) and have pathological confirmation of LGG and determination of BRAF characteristics from the Hospital for Sick Children. Exceptions will be made for patients with neurofibromatosis type 1 who have not previously had a biopsy. NF1 patients are eligible without tissue confirmation but must have definitive clinical or radiographic evidence of tumour progression or risk for significant neurologic deterioration requiring immediate therapy. If a tissue sample for NF1 patients is available from a previous biopsy, it is required to be submitted for Central Review at the Hospital for Sick Children. Please refer to the lab manual for further details.
- Patients must have progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (< 95% or > 1.0 cm2 residual tumour) with necessity to begin treatment because of a risk of neurological impairment with progression.
- All patients on study must have measurable tumour (>1.0 cm2 of residual tissue if resection has been performed) within 28 days of enrollment.
- Patients must have received no prior therapy including chemotherapy, biological modifiers and/or radiation treatment for the tumour with the exception of surgery.
- Patient is able to start treatment within 14 working days after randomization.
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- Post pubertal teenagers who are sexually active agree to use two methods of contraception during the treatment period and for at least 6 months after the last dose of study drug. Please refer to Appendix V for a list of acceptable methods of contraception.
- Lansky performance status > 50% for patients < 16 years of age. Karnofsky performance status > 50% for patients ≥ 16 years of age.
- Patients with neurologic deficits must have deficits that are stable for a minimum of 1 week prior to enrollment.
- Patients receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment.
- Life expectancy > 2 months at the time of enrollment.
- Parents/guardians must provide written informed consent and to agree that they (and the patient) will comply with the study protocol.
- Written assent by patient according to institutional guidelines.
- Patients must have adequate bone marrow function within 2 weeks prior to enrollment:
- Hemoglobin ≥ 10 g/dL (may be supported )
- Neutrophil count ≥ 1.0 × 109/L
- Platelet count ≥ 100 × 109/L (transfusion independent)
- Patients not on a therapeutic dose of an anti-coagulant must have an INR ≤ 1.5 and an aPTT ≤ 1.5x institutional ULN for age within 2 weeks prior to enrollment. Anti-coagulation is permitted prior to enrollment on the condition that the patient is, according to the local clinical practice guidelines or approved product labeling, adequately anti-coagulated prior to enrollment.
- Patients must have satisfactory liver function within 2 weeks prior to enrollment:
- AST ≤ 3x institutional ULN for age
- ALT ≤ 3x institutional ULN for age
- Total Bilirubin ≤ 1.5x institutional ULN for age
- Patients must have satisfactory renal parameters and meet the following criteria within 2 weeks prior to enrollment :
- Serum creatinine must be ≤ 1.5x ULN for age. If the serum creatinine is > 1.5 × ULN, the glomerular filtration rate (either estimated or formal) must be >90 mL/min/1.73 m2, for patient to be enrolled.
- Absence of clinically significant proteinuria, as defined by screening of the early morning urine (urine protein < 1g/L and/or albumin/creatinine ratio < 1.0 (mg/mmol)). If urine protein ≥ 1g/L, then Urine Protein Creatinine (UPC) ratio should be calculated. If UPC ratio > 0.5, 24-hour urine protein should be obtained and the level should be < 1000 mg/24 hours for patient enrollment. Note: UPC ratio of spot urine is an estimation of the 24 urine protein excretion - a UPC ratio of 1 is roughly equivalent to a 24-hour urine protein of 1 g. UPC ratio is calculated using one of the following formulas:
- [urine protein]/[urine creatinine] - if both protein and creatinine are reported in mg/dL or [(urine protein) x0.088]/[urine creatinine] - if urine creatinine is reported in mmol/L
- Quality of Life Correlative Study Inclusion Criteria (Optional):
- Age ≥ 3 and < 18 years.
- English- or Spanish-speaking.
- No known history of a significant neurodevelopmental disorder prior to diagnosis of LGG (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation). Patients with NF1 are not excluded.
- No significant motor or sensory impairment that would prevent computer use and perception of the visual and auditory test stimuli.
Who cannot join
- Children under 6 months of age.
- Pregnant or lactating females.
- Use of any investigational agent, systemic, targeted or immunotherapy prior to the first dose of study treatment.
- Any bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation).
- Patients with evidence of new symptomatic CNS hemorrhage (> grade I) on baseline MRI.
- Any significant cardiovascular disease, e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis, CVAs, transient ischemic attacks (TIAs), and systemic hypertension (i.e., a systolic and diastolic BP ≥ 95th percentile for age, sex), prior history of hypertensive crisis or hypertensive encephalopathy or stroke, uncontrolled cardiac arrhythmia within 6 months prior to enrollment .
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- Any previous venous thromboembolism Grade 3 or higher (NCI CTCAE v. 4.03).
- History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
- Unresolved infection.
- An active peptic or duodenal ulcer.
- Major surgical procedure (see Table 3 section 6.1.7), brain surgery, open biopsy or significant traumatic injury within 28 days prior to enrollment or the anticipation of the need for major (elective) surgery during the course of the study treatment.
- Intermediate surgical procedure (see Table 3 section 6.1.7) within 2 weeks of enrollment.
- Minor surgical procedures (see Table 3 section 6.1.7) within 3 days prior to the start of treatment (including the placement of a central line, including PICC line). Insertion of a port-a-cath will require a 7-day interval prior to the start of treatment.
- Non-healing surgical wound.
- A bone fracture that has not satisfactorily healed.
- Concomitant use of the following:
- Aspirin (> 325mg/day) within 10 days of enrollment
- Clopidogrel (> 75mg/day) within 10 days of enrollment
- Use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes with INR and aPTT outside therapeutic standards according to institutional guidelines within 10 days of first dose of Bevacizumab. Note: 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 institution) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of the Baseline Visit. Prophylactic use of anticoagulants is allowed.
- Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.
Trial locations and contacts
21 sites in 4 countries.
21 sites in 4 countries
Canada10 sites
Alberta Children's Hospital
Calgary, Alberta
Stollery Children's Hospital
Edmonton, Alberta
McMaster Children's Hospital
Hamilton, Ontario
Children's Hospital - London Health Sciences Centre
London, Ontario
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec
Montreal Children's Hospital
Montreal, Quebec
CHU du Quebec-Universite Laval
Québec, Quebec
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
BC Children's Hospital
Vancouver, British Columbia
Cancer Care Manitoba
Winnipeg, Manitoba
United States5 sites
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children's Hospital Colorado
Aurora, Colorado, 80045
Children's Hospital Los Angeles
Los Angeles, California, 90027
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Australia5 sites
Perth Children's Hospital
Nedlands, Western Australia
Women's and Children's Hospital
North Adelaide, South Australia
Royal Children's Hospital
Parkville, Victoria
Queensland Children's Hospital
South Brisbane, Queensland
Children's Hospital at Westmead
Westmead, New South Wales
About this study
Official title: A Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children With Unresectable or Progressive Low Grade Glioma (LGG)
This is an open-label, randomized, multi-center, comparator Phase II trial looking at the addition of Bevacizumab to Vinblastine in chemotherapy naïve pediatric patients with progressive Low Grade Glioma aged 6 months to less than18 years of age at the time of initiation of therapy. Participants will be randomized to Arm A or Arm B. Arm A includes 68 weeks of single agent Vinblastine administered once weekly IV. Arm B includes 68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks. Randomization will take place at the time of registration taking into account NF1 and BRAF-KIAA1549-fusion status.
- Conditions
- Low Grade Glioma
- Being tested
- Vinblastine, Bevacizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VinblastineDrug
BevacizumabDrug
Also called Avastin
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | 68 weeks of single agent Vinblastine administered once weekly IV Receives: Drug: Vinblastine |
| Arm B | Experimental | 68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks. Receives: Drug: Vinblastine; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of the addition of Bevacizumab to Vinblastine compared with Vinblastine alone in chemotherapy-naïve pediatric patients with unresectable or progressive Low Grade Gliomas as measured by Response Rate (RR).
Objective response rate within 6 months of randomisation
Measured: 6 months from randomization
Secondary outcomes (6)
Overall survival (OS) at the end of study.
overal survival at 5 years post randomisation
Measured: From the date of study completion (approximately 6.5 years (78 months)) up till the date of death.
To determine 6 month, 12 month and 2 year progression free survival (PFS) between vinblastine alone versus in combination with Bevacizumab.
Optical Coherence Tomography (OCT) should occur in conjunction with the Visual Field/Acuity exams for participating institutions equipped with OCT.
Measured: At 6 and 12 months and 2 years
To evaluate the difference in visual outcome measures in children with optic pathway gliomas treated with vinblastine alone or in combination with Bevacizumab.
visual acuity measure with Teller Grading Acuity
Measured: Every 3 months during treatment, every 3 months for 1 year after completion of treatment, then every 6 months for 4 years.
To determine if the prevalence of cognitive deficits in children and adolescents treated for LGG, is significantly higher than the normative population (> 14%) using the NIH Toolbox Cognitive Battery.
Domains include: working memory, executive function, processing speed, episodic memory, and attention
Measured: At 1 year off therapy
To determine the effects of Bevacizumab on cognitive function in the pediatric population using the NIH Toolbox Cognitive Battery.
The effects of Bevacizumab on cognitive function in the pediatric
Measured: During treatment, 28 days after completing treatment, at 6 months and 1 year off therapy
To determine if the prevalence of QOL difficulties in children and adolescents treated for LGG at 1 year off therapy, is significantly higher than the normative population (> 14%).
Domains include: fatigue, physical activity, anxiety, depression, and peer relationships.
Measured: At 1 year off therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2016 (estimated)
- Study start1 Aug 2016
- Primary completion31 Jul 2024 (estimated)
- Study completionAug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Low Grade GliomaStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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
- Randomised
- Intervention model
- Crossover
- Model description
- Cross over to bevacizumab-vinblastine allowed in case of progression on vinblastine only
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Responsible party
- Principal investigator, Eric Bouffet, The Hospital for Sick Children
- Investigators
- Eric Bouffet, MD, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02840409
- Sponsor's protocol ID
- 1000052116
- Status last verified
- Jan 2024
- First submitted
- 28 Jan 2016
- Last updated
- 31 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-Labeled, Multi-Center, Randomized Controlled Trial of Vinblastine +/- Bevacizumab for the Treatment of Chemotherapy-Naïve Children With Unresectable or Progressive Low Grade Glioma (LGG)
- ClinicalTrials.gov ID
- NCT02840409
- Acronym / sponsor ID
- 1000052116
- Conditions
- Low Grade Glioma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 109 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- 1 Aug 2016 (actual)
- Primary completion
- 31 Jul 2024 (estimated)
- Study completion
- Aug 2026 (estimated)
- First posted
- 21 Jul 2016 (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.
This is an open-label, randomized, multi-center, comparator Phase II trial looking at the addition of Bevacizumab to Vinblastine in chemotherapy naïve pediatric patients with progressive Low Grade Glioma aged 6 months to less than18 years of age at the time of initiation of therapy. Participants will be randomized to Arm A or Arm B. Arm A includes 68 weeks of single agent Vinblastine administered once weekly IV. Arm B includes 68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks. Randomization will take place at the time of registration taking into account NF1 and BRAF-KIAA1549-fusion status.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Cross over to bevacizumab-vinblastine allowed in case of progression on vinblastine only
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Vinblastine68 weeks of single agent Vinblastine administered once weekly IV |
| Arm B | Experimental | Drug: Vinblastine, Drug: Bevacizumab68 weeks of Vinblastine administered weekly IV with the addition of 12 doses of Bevacizumab administered every two weeks IV for the initial 24 weeks. |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (31 listed)
- Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma (See Appendix I).
- All patients must submit tumour tissue (fresh tumour tissue is recommended) and have pathological confirmation of LGG and determination of BRAF characteristics from the Hospital for Sick Children. Exceptions will be made for patients with neurofibromatosis type 1 who have not previously had a biopsy. NF1 patients are eligible without tissue confirmation but must have definitive clinical or radiographic evidence of tumour progression or risk for significant neurologic deterioration requiring immediate therapy. If a tissue sample for NF1 patients is available from a previous biopsy, it is required to be submitted for Central Review at the Hospital for Sick Children. Please refer to the lab manual for further details.
- Patients must have progressive disease following surgical excision based on clear radiological or clinical evidence of progression, or an incomplete excision (< 95% or > 1.0 cm2 residual tumour) with necessity to begin treatment because of a risk of neurological impairment with progression.
- All patients on study must have measurable tumour (>1.0 cm2 of residual tissue if resection has been performed) within 28 days of enrollment.
- Patients must have received no prior therapy including chemotherapy, biological modifiers and/or radiation treatment for the tumour with the exception of surgery.
Key exclusion criteria (20 listed)
- Children under 6 months of age.
- Pregnant or lactating females.
- Use of any investigational agent, systemic, targeted or immunotherapy prior to the first dose of study treatment.
- Any bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation).
- Patients with evidence of new symptomatic CNS hemorrhage (> grade I) on baseline MRI.
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 |
|---|---|---|
| Vinblastine | Drug | Arm A, Arm B |
| BevacizumabAlso: Avastin | Drug | Arm B |
Primary outcome
Efficacy of the addition of Bevacizumab to Vinblastine compared with Vinblastine alone in chemotherapy-naïve pediatric patients with unresectable or progressive Low Grade Gliomas as measured by Response Rate (RR).
Time frame: 6 months from randomization
Objective response rate within 6 months of randomisation
6 secondary outcomes
Overall survival (OS) at the end of study.
Time frame: From the date of study completion (approximately 6.5 years (78 months)) up till the date of death.
To determine 6 month, 12 month and 2 year progression free survival (PFS) between vinblastine alone versus in combination with Bevacizumab.
Time frame: At 6 and 12 months and 2 years
To evaluate the difference in visual outcome measures in children with optic pathway gliomas treated with vinblastine alone or in combination with Bevacizumab.
Time frame: Every 3 months during treatment, every 3 months for 1 year after completion of treatment, then every 6 months for 4 years.
To determine if the prevalence of cognitive deficits in children and adolescents treated for LGG, is significantly higher than the normative population (> 14%) using the NIH Toolbox Cognitive Battery.
Time frame: At 1 year off therapy
To determine the effects of Bevacizumab on cognitive function in the pediatric population using the NIH Toolbox Cognitive Battery.
Time frame: During treatment, 28 days after completing treatment, at 6 months and 1 year off therapy
To determine if the prevalence of QOL difficulties in children and adolescents treated for LGG at 1 year off therapy, is significantly higher than the normative population (> 14%).
Time frame: At 1 year off therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2024.
Related trials for Low Grade Glioma
Active, not recruitingPhase 1/2
Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
Low Grade Glioma, Recurrent Childhood Pilocytic Astrocytoma
RecruitingPhase 3
A Study of the Drugs Selumetinib vs. Carboplatin and Vincristine in Patients With Low-Grade Glioma
Low Grade Astrocytoma, Low Grade Glioma
RecruitingPhase 2
Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
BRAF V600 Mutation, Low-grade Glioma
Active, not recruitingPhase 2
Nivolumab in Patients With IDH-Mutant Gliomas With and Without Hypermutator Phenotype
Glioma, Glioblastoma
Active, not recruitingPhase 3
DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)
Low-grade Glioma, Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma
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.
Eric Bouffet, MD principal investigator
The Hospital for Sick Children
21 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vinblastine and Bevacizumab in people with Low Grade Glioma, run by The Hospital for Sick Children at 21 sites in 4 countries.
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 31 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 31 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Canada, United States, Australia, New Zealand. 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?
Results are not available in the source record.
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?
Efficacy of the addition of Bevacizumab to Vinblastine compared with Vinblastine alone in chemotherapy-naïve pediatric patients with unresectable or progressive Low Grade Gliomas as measured by Response Rate (RR). (time frame: 6 months from randomization). 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 31 Jan 2024.