LOW-GRADE GLIOMA

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

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2012-003005-10-DK

Enrollment

160

Registered

2013-05-08

Start date

2013-06-06

Completion date

Unknown

Last updated

2022-03-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Children, adolescents and young adults with refractory or recurrent low-grade gliomas, and children, adolescents and young adults with neurofibromatosis type 1 and previously untreated low-grade gliomas MedDRA version: 20.0 Level: PT Classification code 10065443 Term: Malignant glioma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10038111 Term: Recurrent cancer System Organ Class: 10029104

Interventions

Product Name: Nilotinib Product Code: AMN107 Pharmaceutical Form: Capsule, hard Current Sponsor code: AMN107 Other descriptive name: NILOTINIB HYDROCHLORIDE MONOHYDRATE Concentration unit: mg milligra

Eligibility

Sex/Gender

All

Inclusion criteria

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 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 9. Adequate cardiac function: 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. F 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 Are the trial subjects under 18? yes Number of subjects for this age range: 160 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: 1. Concomitant anti-tumor treatment 2. Not recovered to 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 (e.g. unstable angina, congestive heart failure or uncontrolled hypertension). • History of or presence of clinically significant ventricular or atrial tachyarrhythmias (including congenital long QT syndrome or a known family history of congenital long QT syndrome) 11. Positive rest for Hepatitis B virus surface antigen

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase II part: to evaluate the efficacy of vinblastine in combination with nilotinib (VINILO) at the RD, as compared to vinblastine alone, in terms of progression-free survival, in children, adolescents, and young adults with refractory or recurrent low grade glioma and in NF1 patients with low grade glioma at diagnosis.;Secondary Objective: 1. To measure the impact of the VINILO combination compared to vinblastine alone, in terms of tumor response, functionnal status (visual acuity…), progression-free survival time ratio (PFS2/PFS1-ratio), and overall survival (OS) 2. To describe and compare, on the whole duration of treatment, the acute toxicity related to the VINILO combination with that of vinblastine alone; and to compare the long-term effects of both regimens 3. To describe the feasibility of the treatment and the compliance 4. To provide pharmacokinetics data on both drugs when given in combination 5. To identify the predictive value of early functional MRI changes 6. To assess the inter-observers agreement of radiologic response assessment;Primary end point(s): Phase II part – Efficacy assessment PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death). The ;Timepoint(s) of evaluation of this end point: PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death).	—

Measure

Time frame

Main Objective: Phase II part: to evaluate the efficacy of vinblastine in combination with nilotinib (VINILO) at the RD, as compared to vinblastine alone, in terms of progression-free survival, in children, adolescents, and young adults with refractory or recurrent low grade glioma and in NF1 patients with low grade glioma at diagnosis.;Secondary Objective: 1. To measure the impact of the VINILO combination compared to vinblastine alone, in terms of tumor response, functionnal status (visual acuity…), progression-free survival time ratio (PFS2/PFS1-ratio), and overall survival (OS) 2. To describe and compare, on the whole duration of treatment, the acute toxicity related to the VINILO combination with that of vinblastine alone; and to compare the long-term effects of both regimens 3. To describe the feasibility of the treatment and the compliance 4. To provide pharmacokinetics data on both drugs when given in combination 5. To identify the predictive value of early functional MRI changes 6. To assess the inter-observers agreement of radiologic response assessment;Primary end point(s): Phase II part – Efficacy assessment PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death). The ;Timepoint(s) of evaluation of this end point: PFS computed as the time interval between the date of study entry and the date of tumor progression or death (whatever the cause of death).

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Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: over the whole study duration;Secondary end point(s): 1) Safety monitoring during the treatment Clinical and laboratory toxicities / symptoms will be graded according to NCI-CTCAE v4.0 over the whole treatment duration 2) Efficacy criteria Tumor response will be based on two-dimension measurement and to RANO Criteria. All tumor reduction >25% (CR or PR or MR) will be considered as success. Growth modulation index or progression-free survival time ratio (PFS2/PFS1-ratio), defined as the ratio of a patient’s progression-free survival time from start of study treatment (VINILO or Vinblastine alone), PFS2, relative to the progression-free survival time observed from the patient’s most recent prior anticancer treatment, PFS1, which serves as the patient-specific historical control value. Modification of functionnal status. In particular, for optic pathway glioma, quantitative assessment of visual acuity and qualitative changes in visual field will be assessed. Overall survival computed from the date of study entry to the date of death, from any cause. 3) Dose intensity of each drug computed on the whole treatment duration and per month. Duration of treatment and reasons for the end of treatment. 4) Pharmacokinetics dosage of both drugs (for 30 patients of each arm of the phase II part) 5) Functional MRI (perfusion sequence). This dynamic imaging technique will be performed with contrast after 1 month of treatment 6) Tumor biomarkers will be studied on paraffin tumor samples 7) Pharmacogenetic biomarker (enzyme polymorphism) 8) Long-term follow-up: height, weight, pubertal growth, phospho-calcic evaluation and cardiac function	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: over the whole study duration;Secondary end point(s): 1) Safety monitoring during the treatment Clinical and laboratory toxicities / symptoms will be graded according to NCI-CTCAE v4.0 over the whole treatment duration 2) Efficacy criteria Tumor response will be based on two-dimension measurement and to RANO Criteria. All tumor reduction >25% (CR or PR or MR) will be considered as success. Growth modulation index or progression-free survival time ratio (PFS2/PFS1-ratio), defined as the ratio of a patient’s progression-free survival time from start of study treatment (VINILO or Vinblastine alone), PFS2, relative to the progression-free survival time observed from the patient’s most recent prior anticancer treatment, PFS1, which serves as the patient-specific historical control value. Modification of functionnal status. In particular, for optic pathway glioma, quantitative assessment of visual acuity and qualitative changes in visual field will be assessed. Overall survival computed from the date of study entry to the date of death, from any cause. 3) Dose intensity of each drug computed on the whole treatment duration and per month. Duration of treatment and reasons for the end of treatment. 4) Pharmacokinetics dosage of both drugs (for 30 patients of each arm of the phase II part) 5) Functional MRI (perfusion sequence). This dynamic imaging technique will be performed with contrast after 1 month of treatment 6) Tumor biomarkers will be studied on paraffin tumor samples 7) Pharmacogenetic biomarker (enzyme polymorphism) 8) Long-term follow-up: height, weight, pubertal growth, phospho-calcic evaluation and cardiac function

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Countries

Denmark, France, Netherlands, Spain, Switzerland

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026