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

Low-Grade Glioma Clinical Trial

— OVIMA-1210  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197637
• Other study ID #: OVIMA-1210
• Secondary ID: 2013-001625-12PH
• Status: Completed
• Phase: Phase 2
• Start date: May 2014
• Est. completion date: October 2020

Study information

• Verified date: November 2020
• Source: Centre Oscar Lambret
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: October 2020
• Est. primary completion date: August 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Glioma
• Low-Grade Glioma

Intervention

Drug:
• 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 If on D8 and D15, the administration conditions are not met, the administration is canceled and not delayed.

Locations

Country	Name	City	State
France	CHU d'Angers	Angers
France	CHU de Bordeaux	Bordeaux
France	CHU de Grenoble	Grenoble
France	Centre Oscar Lambret	Lille
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	Hôpital de la TIMONE	Marseille
France	CHRU Arnaud de Villeneuve	Montpellier
France	CHU de Nancy	Nancy
France	Institut Curie	Paris
France	CHU de Reims	Reims
France	CHU de Rennes - Hôpital Sud	Rennes
France	CHU de Rouen	Rouen
France	Hôpital Hautepierre	Strasbourg
France	Hôpital des Enfants	Toulouse
France	Institut Gustave Roussy	Villejuif

Sponsors (3)

Lead Sponsor	Collaborator
Centre Oscar Lambret	National Cancer Institute, France, Pierre Fabre Laboratories

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression free survival	no progressive disease according to RANO criteria	9 months
Secondary	Response rate	Complete, partial and minor responses according to RANO criteria	6 months
Secondary	Response rate	Complete, partial and minor responses according to RANO criteria	12 months
Secondary	Progression Free Survival PFS	No progressive disease according to RANO criteria	36 months
Secondary	Overall Survival OS	Death incidence	36 months
Secondary	Growth Modulation Index GMI	GMI defined as PFS2/ PSF1 ratio (PFS2 = PFS since the beginning of study treatment ; PFS1 = PFS observed in previous line of treatment)	36 months
Secondary	Adverse events	According to NCI-CTC AE scale v4.0	12 months
Secondary	Modifications of tumor aspects in diffusion and perfusion MRI	Cerebral and/or spinal MRI (morphological and functional) with 2 dimensional assessment of target lesions.	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
Secondary	Constitutional polymorphisms of cyp3A5, ABCB1	Single nucleotide polymorphisms (SNPs) will be analyzed by real time PCR and correlated with efficacy and toxicity of vinorelbine	Before the start of treatment
Secondary	Pharmacokinetic	Plasmatic concentrations measured by LC-MS/MS (liquid chromatography tandem mass spectrometry) ; Area under the curve (AUC), maximal concentration (Cmax), time to Cmax (Tmax).	cycles 1 and 2, prior to the initial dose, 30 min, 1, 1.5, 2, 3, 6, 8, 10 and 26 hours post-dose
Secondary	Medical costs	Costs of medical care including : hospitalisations, emergency admissions, nursing care at home, medical consultations, diet support...	during all the study (up to 1 year)
Secondary	Health Utilities Index (HUI)	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)