Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma

Inclusion Criteria:

TUMOR CHARACTERISTICS:

* Histologically confirmed recurrent or progressive primary Low-Grade Glioma (LGG) defined as follow (WHO classification 2007): optic pathway glioma (OPG), pilocytic astrocytoma (PA), fibrillary or diffuse astrocytoma (DA), oligodendroglioma (OG) or oligoastrocytoma (OA)
* Patients with OPG do not require biopsy confirmation of disease, if clinical and radiological findings as well as ophthalmological examination are unequivocal
* Low-Grade Glioma involving the brainstem can be included in case of histological confirmation
* Tumor has to be considered as non totally resectable

PATIENT CHARACTERISTICS:

* Age 6-18 years old
* Lansky or Karnofsky status more than 50 %
* Measurable disease on cerebral and/or spinal MRI, with at least 1 lesion diameter superior to 1 cm
* Patients with metastatic disease are eligible, but at least 1 lesion must be measurable as previously defined
* Patients must have received at least 1 prior chemotherapy regimen containing carboplatin
* Life expectancy of at least 3 months
* Evidence of adequate organ functions, including:
* neutrophil count (ANC) ≥ 1500/mm3 ,
* platelet count ≥100 000/mm3 ;
* serum creatinine \< 1.5 x normal for age when the serum creatinine is ≥ 1.5 × the ULN, the glomerular filtration rate (either estimated or formal) must be \> 70 mL/min/1.73m2;
* total bilirubin\< 1.5 x normal for age,
* ASAT and ALAT \< 2.5 x normal for age
* Effective contraception for patients (male and female) with reproductive potential, and for a minimum of 3 months after the end of treatment
* Negative pregnancy test, if applicable
* Patients able to swallow capsules
* Patient affiliated with a health insurance system
* Written informed consent of patient and/or parents/guardians prior to the study participation.

PRIOR OR CONCURRENT THERAPY

* Prior treatments containing vinca alkaloids like vincristine and/or vinblastine are authorized
* Patients must have fully recovered from the toxic effects of any prior therapy before entering the study. No organ toxicity superior to grade 2 according to NCI-CTCAE v4.0
* An interval of at least 2 months from prior radiotherapy, 6 weeks from nitrosourea chemotherapy, and 4 weeks from other chemotherapy regimen, is required

Exclusion Criteria:

* Inclusion criteria failure
* Prior treatment with intravenous or oral vinorelbine
* Known hypersensibility to other vinca-alkaloïdes
* Digestive pathology affecting absorption in a important way
* Prior surgical resection of stomach or the small intestine
* Severe hepatic failure independent from tumoral disease
* Fructose intolerance
* Leptomeningeal relapse without any available measurable disease on MRI (for example, leptomeningeal relapse with totally resected primary lesion)
* Uncontrolled active infection within 2 weeks
* Pregnancy or breast feeding woman
* Uncontrolled intercurrent illness or active infection
* Unsuitable for medical follow-up (geographic, social or mental reasons)
* Patients requiring long-term oxygen therapy
* Patients with ANC less than 1500/mm3
* Patients vaccinated against yellow fever