Vinorelbine for Children With Progressive or Recurrent Low-grade Gliomas

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