R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
Status:
Completed
Trial end date:
2009-02-19
Target enrollment:
Participant gender:
Summary
This study will examine whether the experimental drug R115777 (Tipifarnib) 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 neurofibromin. Neurofibromin is
thought to help control the activity of another protein, called ras, which regulates cell
growth. Too little neurofibromin, 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.