Sorafenib to Treat Children and Young Adults With Neurofibromatosis Type 1 and Inoperable Plexiform Neurofibromas

Summary

Background:

Patients with neurofibromatosis type 1 are at increased risk of developing tumors called plexiform neurofibromas (PN) that arise from nerves. These tumors are usually non-cancerous, but they can cause serious medical problems.

Sorafenib was recently approved to treat patients with kidney cancer and is now being tested in children with cancer. It affects several pathways thought to be important for the development and growth of PN and may therefore shrink these tumors or slow their growth.

Objectives:

To determine the highest dose of sorafenib that can safely be given to children and young adults with PN.

To identify the side effects of sorafenib in these patients.

To study how the body handles sorafenib by measuring the amount of drug in the bloodstream over time

To determine how the drug affects blood flow and blood cells and proteins.

To determine if sorafenib can shrink or slow the growth of PN.

To determine the effects of sorafenib on learning, attention, memory, and quality of life.

Eligibility:

Patients between 3 and 18 years of age with NF1 who have inoperable PN that can cause significant disability.

Design:

Patients take sorafenib tablets twice a day in 28-day treatment cycles. They may continue treatment until their tumor grows or they develop unacceptable drug side effects. In this dose escalation study, the dosage is increased with every 3 to 6 children who are enrolled until the highest safe dose is determined. In any case, the dose will not exceed that used in children with cancer.

Patients are monitored regularly with physical examinations, blood and urine tests, MRI scans and quality-of-life questionnaires.

Patients whose bones are still growing have periodic x-rays of the hips and lower legs to monitor for possible changes in the structure of growing bones.

Patients have periodic tests of learning and memory before starting treatment and before cycles 4, 12, 18 and 24.

Patients have pharmacokinetic studies to examine how the body handles sorafenib. blood samples are drawn before the first dose of sorafenib and then at 30 minutes, 1 hour, 2 hours, 3 hours, 5 hours, 8 hours, 10 to 12 hours, 24 hours and 30 to 36 hours following the first dose.

...

Conditions

• Neurofibromatosis Type I
• Plexiform Neurofibroma

Interventions

DRUG

Nexavar (BAY 43-9006) (Sorafenib)

DRUG

Toxicity, Pharmacokinetics

DRUG

Pharmacodynamics

DRUG

Radiographic Evaluation

DRUG

QOL assessment, Neuropsychological

DRUG

Bony Toxicity

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Brigitte C Widemann, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

3 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2008-07-08

Primary Completion

2011-06-16

Completion

2011-06-16

Countries

• United States

Study Locations