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

Completed · Phase 1

Conditions studied: Neurofibromatosis Type I, Plexiform Neurofibroma

In brief

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. ...

Key facts

Study ID

NCT00727233

Run by

National Cancer Institute (NCI)

People needed

9

Starts

2008-07-08

Expected to finish

2011-06-16

Last updated by the study team

2019-12-12

Who can join

Age: 3 and older, up to 18. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

• Pregnant or breast-feeding females are excluded due to risks of fetal and teratogenic adverse events as seen animal studies. Pregnancy tests must be obtained prior to enrollment on this study in girls, age 9 or older. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Abstinence is an acceptable method of birth control.
• Sorafenib is predominantly metabolized via CYP3A4, and patients who take cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or Phenobarbital), rifampin, grape fruit, or St. Johns Wort will not be eligible for the trial. Patients must have discontinued these medications at least 7 days prior to enrollment of trial.
• Patients who have had major surgery within the past 3 months are excluded. Patients having minor surgery (i.e., central line placement) within the past 2 weeks are excluded.
• An investigational agent within the past 30 days.
• Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, immunotherapy, or biologic therapy.
• Clinically significant uncontrolled unrelated systemic illness such as serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study.
• Inability to swallow tablets, since tablets cannot be crushed or broken.
• Inability to undergo MRI and/or contraindication for MRI examinations following the MRI protocol (Appendix III). Prosthesis or orthopedic or dental braces that would interfere with volumetric analysis of target PN on MRI.
• Prior treatment with sorafenib.
• Evidence of an optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring treatment with chemotherapy or radiation therapy.
• Patients with a history of arterial or venous thrombosis with in the prior 3 months.
• Patients who experienced significant hemorrhage (hemoptysis, melena, or hematemesis) within the past 2 weeks or with a history of bleeding diathesis.
• Patients with a history of NF1 related cerebral vascular anomaly.
• Patients requiring systemic full dose anticoagulation with systemic thrombolytics, heparin, coumadin, or low molecular weight heparin or other anticoagulants for therapy of active thrombosis within the prior 3 months.
• Patients on anti-hypertensive medications and patients with baseline hypertension (greater than or equal to 95th % for age and gender, see Appendix II) (treated or untreated).

Where it is running

• Children's Hospital of Alabama — Birmingham, Alabama, United States
• National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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