PHASE I-II STUDY OF VINBLASTINE IN COMBINATION WITH NILOTINIB IN CHILDREN, ADOLESCENTS, AND YOUNG ADULTS WITH REFRACTORY OR RECURRENT LOW-GRADE GLIOMA

Recruitment & Eligibility

Status: Pending

Sex: Not specified

Target Recruitment: 8

Inclusion Criteria

1. Written informed consent signed by the patient, or parents or legal
representative and assent of the minor child where appropriate.
2. Age: 6 months to < 21 years of age at time of study entry;
3. Diagnosis: one of the three conditions listed below
• Refractory or recurrent low-grade glioma after at least one first-line
therapy with pathological documentation in non NF1 patients (no further biopsy
is needed at study entry)
• Refractory or recurrent low-grade glioma after at least one first-line
therapy in NF1 patients, with or without pathological documentation. For
patients with NF1 and optic pathway glioma, no biopsy is required to confirm
the radiological diagnosis of the low grade glioma.
• Low grade glioma at diagnosis in NF1 patients when the use of chemotherapy is
considered for the treatment in case of threat to vision or unequivocal
radiological tumor progression. Pathological documentation is advised but not
mandatory.
4. Evaluable Disease on morphologic MRI;
5. Karnofsky performance status score >=70% for patients >12 years of age, or
Lansky score >=70% for patients <=12 years of age, including patients with motor
paresis due to disease.
6. Life expectancy >= 3 months.
7. Administration of stable dose of steroids for at least one week
8. Adequate organ function:
• Adequate hematopoietic function: neutrophils >= 1.0 x 109/L, platelets >= 100
x 109/L; hemoglobin >= 8 g/dL
• Adequate renal function: serum creatinine <= 1.5 x ULN for age. In other
cases where serum creatinine >1.5 ULN according to age. Glomerular filtration
rate or creatinine clearance has to be
> 70ml/min/1.73m2 or > 70% of the expected value.
• Adequate electrolytes levels: potassium, magnesium, phosphate, total calcium
>= Lower Limit of Normal (LLN)
• Adequate hepatic function: total bilirubin <=1.5 x ULN; AST and ALT <=2.5 x ULN.
• Absence of peripheral neuropathy >= grade 2 (Common Toxicity Criteria Adverse
Event, NCI CTCAE v4.0)
9. Adequate cardiac function:
• Shortening Fraction (SF) >= 28% (35% for children <3 years) and Left
Ventricular Ejection Fraction (LVEF) >= 50% at baseline, as determined by
echocardiography;
• Absence of QTc prolongation (QTc QTcF formula) or other clinically significant ventricular or atrial arrhythmia
10. Wash-out period of at least
• 3 weeks in case of preliminary chemotherapy
• 6 weeks in case of nitrosourea-containing chemotherapy
• 2 weeks in the case of treatment with vincristine only
• 6 weeks in case of radiation therapy
11. Possibility of receiving the therapeutic schedule as indicated in the
protocol
12. Patients with reproductive potential must use effective/acceptable birth
method control (as defined per CTFG guidelines) during their treatment and for
up to 90 days after the last dose. Females with reproductive potential must
have a negative pregnancy test <= 7 days before randomization.
13. Patients already treated with one of the two drugs can be enrolled in the
trial provided that rechallenging them with the same drug could be considered
acceptable

Exclusion Criteria

1. Concomitant anti-tumor treatment
2. Not recovered to chemotherapy, immunotherapy or radiotherapy
3. Known intolerance or hypersensitivity to Vinblastine;
4. Existence of another severe systemic disease;
5. Uncontrolled infections not responsive to antibiotics, antiviral medicines,
or antifungal medicines
6. Any concurrent illness which in the opinion of the investigator may
interfere with the treatment and evaluation of the patient
7. Impairment of gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of nilotinib.
8. Simultaneous treatment with strong cytochromes P450 CYP3A4 inhibitors
9. Simultaneous treatment with antiarrythmic drugs and other drugs known to
prolong QT interval
10. Impaired cardiac function including any one of the following
• Clinically significant resting brachycardia
• QTc > 450 msec on baseline ECG. If QTc >450 msec and electrolytes are not
within normal ranges, electrolytes should be corrected and then the patient
re-screened for QTc.
• Other clinically significant uncontrolled heart disease
• History of or presence of clinically significant ventricular or atrial
tachyarrhythmias
11. Positive test for Hepatitis B virus surface antigen

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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