Phase II Trial of Oral Vinorelbine in Children With Recurrent or Progressive Unresectable Low-Grade Glioma (OVIMA-1210)

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.

Study Overview

• Status: Completed
• Conditions: Low-Grade Glioma
• Intervention / Treatment: Drug: ORAL VINORELBINE

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.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Angers, France, 49033
    • CHU d'Angers
  • Bordeaux, France, 33076
    • CHU de Bordeaux
  • Grenoble, France, 38043
    • CHU de Grenoble
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Limoges, France, 87042
    • CHU de Limoges
  • Lyon, France, 69373
    • Centre Leon Berard
  • Marseille, France, 13385
    • Hopital De La Timone
  • Montpellier, France, 34000
    • CHRU Arnaud de Villeneuve
  • Nancy, France, 54500
    • CHU de NANCY
  • Paris, France, 75005
    • Institut Curie
  • Reims, France, 51100
    • CHU de Reims
  • Rennes, France, 35203
    • CHU de Rennes - Hôpital Sud
  • Rouen, France, 76031
    • CHU de Rouen
  • Strasbourg, France, 67098
    • Hôpital Hautepierre
  • Toulouse, France, 31059
    • Hopital Des Enfants
  • Villejuif, France, 94805
    • Institut Gustave Roussy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	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.; Other Names: NAVELBINE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	no progressive disease according to RANO criteria	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Complete, partial and minor responses according to RANO criteria	6 months
Response rate	Complete, partial and minor responses according to RANO criteria	12 months
Progression Free Survival PFS	No progressive disease according to RANO criteria	36 months
Overall Survival OS	Death incidence	36 months
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
Adverse events	According to NCI-CTC AE scale v4.0	12 months
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
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
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
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)
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)

Collaborators and Investigators

• Sponsor: Centre Oscar Lambret
• Collaborators: National Cancer Institute, France; Pierre Fabre Laboratories
• Investigators: Principal Investigator: Pierre LEBLOND, MD, PhD, Centre Oscar Lambret, Lille, France; Principal Investigator: Nicolas ANDRE, MD, PhD, Hôpital La Timone, Marseille, France

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: May 9, 2014
• First Submitted That Met QC Criteria: July 21, 2014
• First Posted (Estimate): July 23, 2014

Study Record Updates

• Last Update Posted (Actual): November 18, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vinorelbine
• Other Study ID Numbers: OVIMA-1210; 2013-001625-12 (EudraCT Number); PHRC 12- 194 (Other Grant/Funding Number: INCA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No