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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02840409


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT02840409
Ethics application status
Date submitted
28/01/2016
Date registered
21/07/2016
Date last updated
13/03/2020

Titles & IDs
Public title
Vinblastine +/- Bevacizumab in Children With Unresectable or Progressive Low Grade Glioma (LGG)
Scientific 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)
Secondary ID [1] 0 0
1000052116
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Low Grade Glioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Vinblastine
Treatment: Drugs - Bevacizumab

Active Comparator: Arm A - 68 weeks of single agent Vinblastine administered once weekly IV

Experimental: 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.


Treatment: Drugs: Vinblastine


Treatment: Drugs: Bevacizumab


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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).
Timepoint [1] 0 0
6 months from randomization
Secondary outcome [1] 0 0
Overall survival (OS) at the end of study.
Timepoint [1] 0 0
From the date of study completion (approximately 6.5 years (78 months)) up till the date of death.
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
At 6 and 12 months and 2 years
Secondary outcome [3] 0 0
To evaluate the difference in visual outcome measures in children with optic pathway gliomas treated with vinblastine alone or in combination with Bevacizumab.
Timepoint [3] 0 0
Every 3 months during treatment, every 3 months for 1 year after completion of treatment, then every 6 months for 4 years.
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
At 1 year off therapy
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
During treatment, 28 days after completing treatment, at 6 months and 1 year off therapy
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
At 1 year off therapy

Eligibility
Key inclusion criteria
1. Children and adolescents aged 6 months to < 18 years old with Low Grade Glioma (See
Appendix I).

2. 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.

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 tumour) with necessity to begin treatment because of a risk of
neurological impairment with progression.

4. All patients on study must have measurable tumour (>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 tumour 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. Please refer to Appendix V for a list of acceptable methods of
contraception.

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 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):

1. Age = 3 and < 18 years.

2. English- or Spanish-speaking.

3. 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.

4. No significant motor or sensory impairment that would prevent computer use and
perception of the visual and auditory test stimuli.
Minimum age
6 Months
Maximum age
18 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 (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.

12. Intermediate surgical procedure (see Table 3 section 6.1.7) within 2 weeks of
enrollment.

13. 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.

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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Women's and Children's Hospital - North Adelaide
Recruitment hospital [4] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [5] 0 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
- Westmead
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- North Adelaide
Recruitment postcode(s) [4] 0 0
- Parkville
Recruitment postcode(s) [5] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
Canada
State/province [6] 0 0
Alberta
Country [7] 0 0
Canada
State/province [7] 0 0
British Columbia
Country [8] 0 0
Canada
State/province [8] 0 0
Manitoba
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
New Zealand
State/province [11] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
The Hospital for Sick Children
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Hoffmann-La Roche
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02840409
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Bouffet, MD
Address 0 0
The Hospital for Sick Children
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Emily Taylor
Address 0 0
Country 0 0
Phone 0 0
416-813-7654
Fax 0 0
Email 0 0
emilyl.taylor@sickkids.ca
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02840409

Additional trial details provided through ANZCTR
Accrual to date
11
Recruiting in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruiting in New Zealand
Province(s)/district(s)
Starship Hospital
Funding & Sponsors
Primary sponsor
Primary sponsor name
Primary sponsor address
Primary sponsor country
Secondary sponsor category [1] 27
Other Collaborative groups
Name [1] 27
ANZCHOG
Address [1] 27
27-31 Wright Street, Clayton VIC 3168
Country [1] 27
Australia
Ethics approval
Ethics application status
 
Public notes
Children's Hospital Westmead
Perth Children's Hospital
Queensland Children's Hospital
Royal Children's Hospital
Women's and Children's Hospital

Contacts
Principal investigator
Title 137 0
A/Prof
Name 137 0
Jordan Hansford
Address 137 0
50 Flemington Rd, Parkville VIC 3052
Country 137 0
Australia
Phone 137 0
Fax 137 0
Email 137 0
Jordan.Hansford@rch.org.au
Contact person for public queries
Title 138 0
Mrs
Name 138 0
Robyn Strong
Address 138 0
27-31 Wright Street, Clayton VIC 3168
Country 138 0
Australia
Phone 138 0
+613 8572 2684
Fax 138 0
+613 9902 4810
Email 138 0
Robyn.Strong@hudson.org.au
Contact person for scientific queries
Title 139 0
A/Prof
Name 139 0
Jordan Hansford
Address 139 0
50 Flemington Rd, Parkville VIC 3052
Country 139 0
Australia
Phone 139 0
Fax 139 0
Email 139 0
Jordan.Hansford@rch.org.au