Low-Grade Glioma
Conditions
Brief summary
The purpose of this study is to determine whether oral vinorelbine is effective in the treatment of children with progressive or recurrent unresectable low grade glioma.
Detailed description
The aim of this study is to determine efficacy of oral vinorelbine in children with progressive or recurrent unresectable low grade glioma, in addition to safety, pharmacokinetic, pharmacogenetic, medical costs and quality of life.
Interventions
DRUGORAL VINORELBINE
Orally vinorelbine 60 mg/m2 D1, 8 and 15 Cycle of 28 days For a maximum of 12 cycles The dose of vinorelbine should be increased to 80 mg/m2 from the 2nd cycle If on D8 and D15, the administration conditions are not met, the administration is canceled and not delayed.
Sponsors
National Cancer Institute, France
Pierre Fabre Laboratories
Centre Oscar Lambret
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival | 9 months | no progressive disease according to RANO criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival PFS | 36 months | No progressive disease according to RANO criteria |
| Overall Survival OS | 36 months | Death incidence |
| Growth Modulation Index GMI | 36 months | GMI defined as PFS2/ PSF1 ratio (PFS2 = PFS since the beginning of study treatment ; PFS1 = PFS observed in previous line of treatment) |
| Adverse events | 12 months | According to NCI-CTC AE scale v4.0 |
| Response rate | 6 months | Complete, partial and minor responses according to RANO criteria |
| Constitutional polymorphisms of cyp3A5, ABCB1 | Before the start of treatment | Single nucleotide polymorphisms (SNPs) will be analyzed by real time PCR and correlated with efficacy and toxicity of vinorelbine |
| Pharmacokinetic | cycles 1 and 2, prior to the initial dose, 30 min, 1, 1.5, 2, 3, 6, 8, 10 and 26 hours post-dose | Plasmatic concentrations measured by LC-MS/MS (liquid chromatography tandem mass spectrometry) ; Area under the curve (AUC), maximal concentration (Cmax), time to Cmax (Tmax). |
| Medical costs | during all the study (up to 1 year) | Costs of medical care including : hospitalisations, emergency admissions, nursing care at home, medical consultations, diet support... |
| Health Utilities Index (HUI) | Before the treatment, then at day 1 of 1st cycle, after the 3th, 6th, 9th and the 12th cycles of study treatment, and at the end of study (up to 1 year) | Health Utilities Index (HUI) |
| Modifications of tumor aspects in diffusion and perfusion MRI | At each tumor assessment, after 3, 6, 9 and 12 cycles of treatment, at the end of study, then every 4 months during the first year post therapy, then every 6 months for 3 years, if no prior progressive disease | Cerebral and/or spinal MRI (morphological and functional) with 2 dimensional assessment of target lesions. |
Countries
France
Outcome results
None listed