Clinical Trials/NCT02840409

NCT02840409

Active, not recruiting

Phase 2

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)

The Hospital for Sick Children21 sites in 4 countries109 target enrollmentAugust 1, 2016

ConditionsLow Grade Glioma

InterventionsBevacizumab Vinblastine

DrugsVinblastine Bevacizumab

Overview

Phase: Phase 2
Intervention: Bevacizumab
Conditions: Low Grade Glioma
Sponsor: The Hospital for Sick Children
Enrollment: 109
Locations: 21
Primary Endpoint: 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).
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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. 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.

Registry

clinicaltrials.gov

Start Date

August 1, 2016

End Date

August 2026

Last Updated

2 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

The Hospital for Sick Children

Responsible Party

Principal Investigator

Eric Bouffet

Staff Physician, Paediatric Neuro-Oncology Program

The Hospital for Sick Children

Eligibility Criteria

Inclusion Criteria

•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.
•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.

Exclusion Criteria

•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 .
•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.

Arms & Interventions

Arm B

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.

Intervention: Bevacizumab

Arm A

68 weeks of single agent Vinblastine administered once weekly IV

Intervention: Vinblastine

Arm B

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.

Intervention: Vinblastine

Outcomes

Primary Outcomes

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

Secondary Outcomes

To determine 6 month, 12 month and 2 year progression free survival (PFS) between vinblastine alone versus in combination with Bevacizumab.(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.(Every 3 months during treatment, every 3 months for 1 year after completion of treatment, then every 6 months for 4 years.)
Overall survival (OS) at the end of study.(From the date of study completion (approximately 6.5 years (78 months)) up till the date of death.)
To determine the effects of Bevacizumab on cognitive function in the pediatric population using the NIH Toolbox Cognitive Battery.(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%).(At 1 year off therapy)
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.(At 1 year off therapy)