Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma
- Registration Number
- NCT02197637
- Lead Sponsor
- Centre Oscar Lambret
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 39
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ORAL VINORELBINE ORAL 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
- Primary Outcome Measures
Name Time Method Progression free survival 9 months no progressive disease according to RANO criteria
- Secondary Outcome Measures
Name Time Method Response rate 12 months Complete, partial and minor responses according to RANO criteria
Progression Free Survival PFS 36 months No progressive disease according to RANO criteria
Overall Survival OS 36 months Death incidence
Adverse events 12 months According to NCI-CTC AE scale v4.0
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)
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.
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)
Trial Locations
- Locations (16)
Hôpital de la TIMONE
🇫🇷Marseille, France
CHU de Rouen
🇫🇷Rouen, France
Institut Gustave Roussy
🇫🇷Villejuif, France
CHU de Bordeaux
🇫🇷Bordeaux, France
Centre Léon Bérard
🇫🇷Lyon, France
CHU de Nancy
🇫🇷Nancy, France
CHU de Limoges
🇫🇷Limoges, France
Institut Curie
🇫🇷Paris, France
Hôpital Hautepierre
🇫🇷Strasbourg, France
CHU de Reims
🇫🇷Reims, France
CHU d'Angers
🇫🇷Angers, France
Centre Oscar Lambret
🇫🇷Lille, France
CHRU Arnaud de Villeneuve
🇫🇷Montpellier, France
CHU de Rennes - Hôpital Sud
🇫🇷Rennes, France
Hôpital des Enfants
🇫🇷Toulouse, France
CHU de Grenoble
🇫🇷Grenoble, France