low-grade glioma
Conditions
Interventions
Phase I part: Nilotinib and Vinblastine dose-escalation
Nilotinib (Tasigna®): 115 to 350 mg/m2 twice daily (BID) orally given
continuously (115 mg/m2 once daily if de-escalation requested). The
admin
Sponsors
Gustave Roussy
Eligibility
Age
2 Years to 99 Years
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 =70% for patients >12 years of age, or Lansky score >=70% for patients = 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 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 = 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
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 • History of or presence of clinically significant ventricular or atrial tachyarrhythmias 11. Positive test for Hepatitis B virus surface antigen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I part - Safety assessment Dose-Limiting Toxicity (DLT), assessed over the first 28-day cycle, defined as • Grade > 3 neutropenia ( 2 thrombopenia (25% increase in two-dimension measurements or appearance of new lesions compared to the baseline or to the best response after initiation of therapy) or clinically by new symptoms related to tumor progression (significant decrease of visual acuity, new or worsening neurological deficit). Hydrocephalus is not considered as progression per se. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. The adverse events which are not reported in the NCI-CTC will be graded as mild, moderate, severe, and life-threatening. In particular, cardiac function will be monitored with echocardiography and ECG. 2) Efficacy criteria Tumor response will be based on two-dimension measurement and to RANO Criteria (van den Bent, Lancet Oncol 2011). The radiological imaging will be reanalyzed after the study by a radiologist panel, according to the RANO criteria and to the newly defined RAPNO Criteria, once they will be available. All tumor reduction >25% (CR or PR or MR) will be considered as success. Morphologic MRI will be performed every 3 months prior to the new cycle, apart from the week 4 early evaluations in case functional MRI is performed. Primary objective of the study is PFS and thus objective response does not need to be confirmed at 4 to 6 weeks. Baseline MRI and that related to the best response will be centrally reviewed by an independent international radiology panel. 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) | — |
Countries
Netherlands
Outcome results
None listed