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

Centre Oscar Lambret

Status and phase: Completed; Phase 2

Conditions: Low-Grade Glioma

Treatments: Drug: ORAL VINORELBINE

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02197637

PHRC 12- 194 (Other Grant/Funding Number)

2013-001625-12 (EudraCT Number)

OVIMA-1210

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 6 to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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39 participants in 1 patient group

ORAL VINORELBINE

Experimental group

Description:

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

Treatment:

Drug: ORAL VINORELBINE