At a glance
ClinicalIndex Comparison Record- ✓Age 3 to 25 years
- ✓Confirmed NF1 diagnosis with progressive plexiform neurofibroma that is measurable (≥3 cm in one dimension)
- ✓At least one additional NF1 diagnostic criterion besides plexiform neurofibroma (café-au-lait spots, freckling, optic glioma, Lisch nodules, distinctive bony lesion, or first-degree relative with NF1)
- ✓Documented disease progression on imaging within approximately 1 year prior to study entry (20% volume increase, 13% increase in product of two longest perpendicular diameters, or 6% increase in longest diameter)
- ✕Pregnant or breast-feeding females
- ✕Prior treatment with >1 myelosuppressive chemotherapy regimen
- ✕Evidence of optic glioma, malignant glioma, malignant peripheral nerve sheath tumor, or other cancer requiring chemotherapy or radiation
- ✕Ongoing radiation therapy, chemotherapy, hormonal therapy, or immunotherapy directed at tumor
Standardized by ClinicalIndex from the ClinicalTrials.gov record · verify against the source.
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
In Brief
A Phase 2 clinical trial evaluating tipifarnib and placebo for Neurofibroma, Plexiform and Neurofibromatosis Type I. Completed, enrolled 62 participants across 12 sites in 2 countries.
Detailed 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.
Study Details
Timeline
Interventions
Given orally, 200 mg/m\^2/dose BSA every 12 hours by mouth (po) daily x 21 days, Course is every 28 days
Patients receive oral placebo every 12 hours on days 1-21. Courses repeat as in arm I.