R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas

Completed · Phase 2 · Has a placebo group

Conditions studied: Neurofibroma, Plexiform, Neurofibromatosis Type I

In brief

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.

Key facts

Study ID: NCT00021541
Run by: National Cancer Institute (NCI)
People needed: 62
Starts: 2001-07-17
Expected to finish: 2009-02-19
Last updated by the study team: 2018-04-17

Who can join

Age: 3 and older, up to 25. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Pregnant or breast feeding females are excluded, because the toxic effects and pharmacology of R115777 in the fetus and newborn are unknown.
Clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction) which in the judgement of the Principal or Associate Investigator would compromise the patient's ability to tolerate R115777 or are likely to interfere with the study procedures or results.
Prior treatment with greater than 1 prior myelosuppressive chemotherapy regimen.
An investigational agent within the past 30 days.
Evidence of an optic glioma, malignant glioma, malignant peripheral nerve sheath tumor or other cancer requiring treatment with chemotherapy or radiation therapy.
Ongoing radiation therapy, chemotherapy, hormonal therapy directed at the tumor, or immunotherapy.
Inability to return for follow-up visits or obtain follow-up studies required to assess toxicity and response to therapy.
Prior treatment with R115777.

Where it is running

University of Alabama at Birmingham (M1149) — Birmingham, Alabama, United States
Children's Hospital Los Angeles, CA (M1118) — Los Angeles, California, United States
Children's Memorial Hospital, Chicago, IL (M1484) — Chicago, Illinois, United States
Johns Hopkins Oncology Center (M1011) — Baltimore, Maryland, United States
National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States
The Children's Hospital, Dana-Farber Cancer Institute, Boston, MA (M1034) — Boston, Massachusetts, United States
St. Louis Children's Hospital, St. Louis, MO (M1123) — St Louis, Missouri, United States
SUNY Upstate Medical University, NY (M1303) — Syracuse, New York, United States
Cincinnati Children's Hospital (FWA 00002988) — Cincinnati, Ohio, United States
Childrens Hospital of Philadelphia, PA (M1257) — Philadelphia, Pennsylvania, United States
Texas Children's Hospital, Houston, TX (M1060) — Houston, Texas, United States
Klinikum Nord, Hamburg, Germany (FWA 00003228) — Hamburg, Germany

Full record on ClinicalTrials.gov

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