R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
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|ClinicalTrials.gov Identifier: NCT00021541|
Recruitment Status : Completed
First Posted : July 23, 2001
Results First Posted : September 17, 2012
Last Update Posted : April 17, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Neurofibroma, Plexiform Neurofibromatosis Type I||Drug: tipifarnib Other: placebo||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||62 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official 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|
|Actual Study Start Date :||July 17, 2001|
|Actual Primary Completion Date :||February 19, 2009|
|Actual Study Completion Date :||February 19, 2009|
Experimental: Tipifarnib (R11577)-Arm I
Patients receive oral R115777 (Tipifarnib) first followed by placebo. 200 mg/m^2/dose BSA every 12 hours by mouth (po)on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Given orally, 200 mg/m^2/dose BSA every 12 hours by mouth (po) daily x 21 days, Course is every 28 days
Other Name: R115777
Placebo Comparator: Placebo-Arm II
Patients receive oral placebo first followed by R115777 (Tipifarnib). 200 mg/m^2/dose BSA every 12 hours by mouth (po)every 12 hours on days 1-21. Courses repeat as in arm I.
Patients receive oral placebo every 12 hours on days 1-21. Courses repeat as in arm I.
- Median Time to Progression [ Time Frame: 8 years ]Median time to progression is defined as a greater than or equal to 20% increase increase in the sum of the volume of all index lesions based on volumetric analysis utilizing magnetic resonance imaging (MRI).Start of phase A or phase B to time of progression.
- Number of Participants With Adverse Events [ Time Frame: 8 years ]Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
- Quality of Life (QOL) [ Time Frame: Baseline to pre cycle 4 ]Parents of participants aged 6-18 years completed the Impact of Pediatric Illness (IPI) Scale about their child prior to the start of cycles 1, 4, 7, and 10 and then after every 6 cycles. The IPI Scale assesses QOL in 4 domains: adaptive behavior, emotional functioning, medical/physical status, and cognitive functioning. Responses to the 43 items are made on a 5-point Likert scale (1-5) ranging from "not al all" to "a lot". Higher mean scores indicate better QOL. Parent total scores for participants on placebo were compared with scores from participants receiving tipifarnib on phase A.
- Median Time to Progression Using the Conventional 1-Dimensional Response Evaluation Criteria in Solid Tumors (RECIST) Method [ Time Frame: 8 years ]Median time to progression is defined as ≥20% increase in diameter based on volumetric analysis using the 1-dimensional RECIST method. Start of phase A or phase B to time of progression.
- Median Time to Progression Using the 2-Dimensional World Health Organization (WHO) Solid Tumor Method [ Time Frame: 8 years ]Median time to progression is defined as ≥25% increase in area based on volumetric analysis using the 2-dimensional WHO solid tumor method.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00021541
|United States, Alabama|
|University of Alabama at Birmingham (M1149)|
|Birmingham, Alabama, United States, 35233|
|United States, California|
|Children's Hospital Los Angeles, CA (M1118)|
|Los Angeles, California, United States, 90027|
|United States, Illinois|
|Children's Memorial Hospital, Chicago, IL (M1484)|
|Chicago, Illinois, United States, 60614|
|United States, Maryland|
|Johns Hopkins Oncology Center (M1011)|
|Baltimore, Maryland, United States, 21231|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|United States, Massachusetts|
|The Children's Hospital, Dana-Farber Cancer Institute, Boston, MA (M1034)|
|Boston, Massachusetts, United States, 02115|
|United States, Missouri|
|St. Louis Children's Hospital, St. Louis, MO (M1123)|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|SUNY Upstate Medical University, NY (M1303)|
|Syracuse, New York, United States, 13210|
|United States, Ohio|
|Cincinnati Children's Hospital (FWA 00002988)|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Childrens Hospital of Philadelphia, PA (M1257)|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|Texas Children's Hospital, Houston, TX (M1060)|
|Houston, Texas, United States, 77030|
|Klinikum Nord, Hamburg, Germany (FWA 00003228)|
|Hamburg, Germany, D-22419|
|Principal Investigator:||Brigitte Widemann, M.D.||National Insitutes of Health, National Cancer Institute|