Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00021541
Status:
COMPLETED
Last Update Posted:
2018-04-17
First Post:
2006-06-19
Brief Title:
R115777 to Treat Children With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2018-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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
Detailed Description:
R115777 Tipifarnib is a farnesyltransferase inhibitor that blocks the post-translational isoprenylation of ras and other farnesylated proteins The ras proteins are integral in cell signaling pathways and farnesylation is essential for the function of both mutant and non-mutant ras proteins Patients with neurofibromatosis type 1 NF1 have an increased risk of developing tumors of the central and peripheral nervous system and there are no standard treatment options other than surgery available for these tumors Neurofibromin which is the product of the NF1 gene contains a domain with significant homology to ras GTPase-activating proteins GAP Although NF1 patients lack germline ras mutations the decreased levels of neurofibromin have been shown to be associated with a constitutively activated ras-GTP status Thus upstream inhibition of ras farnesylation may inhibit growth of tumors in NF1 patients A randomized cross-over double-blinded placebo-controlled pediatric phase II trial of oral R115777 will be performed in children and young adults with NF1 who have progressive plexiform neurofibromas to determine the effect of this novel anticancer drug on the rate of growth of neurofibromas The endpoint of the trial is time to progression R115777 will be administered orally at a dose of 200 mgm2 twice daily for cycles of 21 days followed by a 7 day rest period based on the results of our prior pediatric phase I trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-C-0222 | None | None | None |