A study to compare the treatment of Vinblastine alone or in combination with Bevacizumab in children with progressive low grade glioma (LGG).

Phase 1

• Conditions: nresectable or progressive low grade glioma; MedDRA version: 20.0 Level: PT Classification code 10018338 Term: Glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001982-26-GB
• Lead Sponsor: The Hospital for Sick Children

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-21
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 150

Inclusion Criteria

1. Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma.
2. All patients must submit tumor tissue (fresh tumor 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 if not available but must have definitive clinical or radiographic evidence of tumor 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.
3. 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 tumor) with necessity to begin treatment because of a risk of neurological impairment with progression.
4. All patients on study must have measurable tumor (> 1.0 cm2 of residual tissue if resection has been performed) within 28 days of enrollment.
5. Patients must have received no prior therapy including chemotherapy, biological modifiers and/or radiation treatment for the tumor with the exception of surgery.
6. Patient is able to start treatment within 14 working days after randomization.
7. 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.
8. Lansky performance status > 50% for patients < 16 years of age. Karnofsky performance status > 50% for patients = 16 years of age.
9. Patients with neurologic deficits must have deficits that are stable for a minimum of 1 week prior to enrollment.
10. Patients receiving corticosteroids must be on a stable or decreasing dose for at least 1 week prior to enrollment.
11. Life expectancy > 2 months at the time of enrollment.
12. Parents/guardians must provide written informed consent and to agree that they (and the patient) will comply with the study protocol.
13. Written assent by patient according to institutional guidelines.
14. 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)
15. 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.
16. 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
17. Patients must have satisfactory rena

Exclusion Criteria

1. Children under 6 months of age.
2. Pregnant or lactating females.
3. Use of any investigational agent, systemic, targeted or immunotherapy prior to the first dose of study treatment.
4. Any bleeding diathesis or significant coagulopathy at risk of bleeding (i.e. in the absence of therapeutic anticoagulation).
5. Patients with evidence of new symptomatic CNS hemorrhage (> grade I) on baseline MRI.
6. 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.
7. Any previous venous thromboembolism Grade 3 or higher (NCI CTCAE v. 4.03).
8. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment.
9. Unresolved infection.
10. An active peptic or duodenal ulcer.
11. Major surgical procedure, 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.
12. Intermediate surgical procedure within 2 weeks of enrollment.
13. Minor surgical procedures 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 days interval prior to the start of treatment.
14. Non-healing surgical wound.
15. A bone fracture that has not satisfactorily healed.
16. 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.
17. Hypersensitivity to Chinese hamster ovary (CHO) cell products or other recombinant human or humanized antibodies.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified