Vinorelbine for Children With Progressive or Recurrent Low-grade Gliomas

Phase 2 Study of Weekly Vinorelbine in Children With Progressive or Recurrent Low-Grade Gliomas

The purpose of this study is to investigate whether weekly Vinorelbine treatment can shrink or slow the growth of pediatric low-grade gliomas that have either returned or are continuing to grow.

Vinorelbine is a semi-synthetic vinca alkaloid that has recently generated interest in patients with pediatric low-grade glioma. It has been specifically synthesized to broaden its therapeutic spectrum and decrease the neurotoxicity associated with related agents.

Different treatments exist for children with progressive or recurrent low-grade glioma. Each has variable efficacy at slowing or reversing growth, and exploration continues into finding better-tolerated, more effective treatments.

Vinorelbine has recently generated interest in stabilizing some pediatric low-grade gliomas. It has been fairly well tolerated in both adult and pediatric studies that have examined its use in other tumors.

Objective: To test the efficacy of Vinorelbine in children with pediatric low-grade glioma that has returned or continues to grow.

In this trial, Vinorelbine will be given intravenously once a week for 6 weeks followed by a 2 week rest (6 of every 8 weeks) for one year. The patients will then be followed for 60 months. Progression free survival is the primary outcome and defined as the none of the following: greater a 20% increase in the sun of the longest diameter of the target lesion, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Inclusion Criteria:

• Age: < 18 years
• Tumor: Progressive or recurrent low grade glioma, WHO grade 1 or 2 who have failed at least one form of 'conventional' non-surgical therapy
• Histologic confirmation is required with the exception of optic pathway and brain stem gliomas. Patients are not required to have a re-operation at time of recurrence.
• Patients with disseminated disease are eligible.
• Children with neuro-fibromatosis and optic pathway or brainstem tumors are eligible but must have definitive radiologic or clinical evidence of progression
• Patients must have evidence of measureable disease
• Performance status: Karnofsky or Lansky performance status of >50%
• Organ Function:
• Adequate bone marrow function (ANC>1000/mm3, platelet count of >75,000/mm3, and hemoglobin > 8gm/dL) prior to starting therapy. Hemoglobin may be supported by transfusion
• Adequate liver function (SGPT/ALT<2.5 times ULN and bilirubin < 1.5 times ULN) prior to starting therapy
• Prior therapy:
• May have had treatment including surgery, chemotherapy, or radiotherapy for any number of relapses prior to enrollment
• Patients must have received their last fraction of radiotherapy >12 weeks prior to starting therapy
• Previous Vincristine or Vinblastine exposure is allowable.

Exclusion Criteria:

• No other significant medical illness that in the investigators' opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
• Any other cancer (except non-melanoma skin cancer), unless in complete remission and off of all therapy for that disease for a minimum of 3 years.
• Patients of childbearing potential must not be pregnant or breast-feeding (vinorelbine is a pregnancy category D, no data on excretion in breastmilk)
• Patients of childbearing or fathering potential must practice adequate contraception