Clinical trial NCT02197637: Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma
Official title: Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Low-Grade Glioma
Lead sponsor: Centre Oscar Lambret
Sponsor class: OTHER
Collaborators: name: National Cancer Institute, France
name: Pierre Fabre Laboratories
First posted: 2014-07-23
Enrollment: 39
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival
timeFrame: 9 months
Secondary outcomes:
measure: Response rate
timeFrame: 6 months
measure: Response rate
timeFrame: 12 months
measure: Progression Free Survival PFS
timeFrame: 36 months
measure: Overall Survival OS
timeFrame: 36 months
measure: Growth Modulation Index GMI
timeFrame: 36 months
measure: Adverse events
timeFrame: 12 months
measure: Modifications of tumor aspects in diffusion and perfusion MRI
timeFrame: 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
measure: Constitutional polymorphisms of cyp3A5, ABCB1
timeFrame: Before the start of treatment
measure: Pharmacokinetic
timeFrame: cycles 1 and 2, prior to the initial dose, 30 min, 1, 1.5, 2, 3, 6, 8, 10 and 26 hours post-dose
measure: Medical costs
timeFrame: during all the study (up to 1 year)
measure: Health Utilities Index (HUI)
timeFrame: 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)
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU d'Angers
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU de Limoges
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Hôpital de la TIMONE
city: Montpellier
country: France
facility: CHRU Arnaud de Villeneuve
city: Nancy
country: France
facility: CHU de Nancy
city: Paris
country: France
facility: Institut Curie
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Sud
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: Hôpital Hautepierre
city: Toulouse
country: France
facility: Hôpital des Enfants
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: Centre Oscar Lambret, Lille, France
name: Pierre LEBLOND, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hôpital La Timone, Marseille, France
name: Nicolas ANDRE, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: