Protocol Number: 01-C-0222

Title:

A Phase II Randomized, Cross-Over, Double-Blinded, Placebo-Controlled Trial of the Farnesyltransferase Inhibitor R115777 in Pediatric Patients with Neurofibromatosis Type I and Progressive Plexiform Neurofibromas

Number:

01-C-0222

Summary:

This study will examine whether the experimental drug R115777 can shrink or slow the growth of plexiform neurofibromas in children and young adults with neurofibromatosis type 1 (NF1) and determine what side effects are related to treatment. Plexiform tumors arise from nerves; the only effective treatment is surgical removal. Often, however, not all the tumors can be removed, because of their number or location.

Patients with NF1 have a reduced amount of the protein neurofibrin. Neurofibrin is thought to help control the activity of another protein, called ras, which regulates cell growth. Too little neurofibrin, therefore, may allow for uncontrolled cell growth and tumor formation. R115777 interferes with the function of the ras and other proteins. In test tube and animal studies, R115777 has blocked the growth of cancer cells. This study will examine whether the drug is effective against plexiform tumors.

Patients with NF1 and progressive plexiform neurofibromas between 3 and 25 years of age may be eligible for this study. Patients whose tumors can be successfully removed surgically may not participate in this study. Candidates are screened with a medical history and physical and eye examinations, blood and urine tests, and magnetic resonance imaging (MRI). Photographs are taken of tumors visible on the body surface.

Study participants are randomly assigned to receive either R115777 or placebo (an inactive substance). They take R115777 or placebo tablets every 12 hours for 21 days, followed by a 7-day rest period. This constitutes one 28-day treatment cycle. Treatment continues for as long as the tumors remain stable or shrink and side effects are tolerable. The treatment is switched (for example, from placebo to R115777) or stopped if the tumors grow or if side effects become unacceptable. Patients (or their parents) keep a record of side effects.

For the first 3 treatment cycles, patients have a physical examination and blood tests every other week. Blood tests are also done before starting treatment, and at one time point after at least 14 days of treatment to measure the effect of R115777 on proteins in blood cells. A blood sample is obtained before starting treatment and before cycles 4, 7 and 10 and then after every 6 cycles to measure the level of a substance called nerve growth factor. The analysis of nerve growth factor is used to determine if it can predict which patients might be at risk of developing side effects from R115777. MRI scans are done periodically throughout treatment to measure the size of the tumors. A tissue biopsy (surgical removal of a small tumor tissue sample) is done before treatment begins and again at least 2 weeks after treatment starts, if tumor nodules are easily accessible for biopsy. Tumor samples may also be obtained from tissue removed from patients who must undergo surgery for medical management of their disease. The tissue samples are analyzed for changes in the NF1 and ras genes and in the ras protein.

Patients (or their parents) are asked periodically throughout the course of treatment to fill out questionnaires assessing quality of life.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Surrogate Markers

3-Dimensional MRI

Natural History of NF1

Tumor Tissue Bank

Recruitment Keyword(s):

Neurofibromatosis

NF1

Neurofibromatosis Type 1

Plexiform Neurofibroma

Neurofibroma

Condition(s):

Neurofibroma, Plexiform

Neurofibromatosis Type I

Investigational Drug(s):

R115777

Investigational Device(s):

None

Interventions:

Drug: R115777

Supporting Site:

National Cancer Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Neurofibromatosis type 1 and Ras-mediated signaling: filling in the GAPs

Patients treated with antitumor drugs displaying neurological deficits are characterized by a low circulating level of nerve growth factor

Neurofibromatosis type 1--an update and review for the primary pediatrician

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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