Ignite Creation Date:
2024-05-05 @ 11:33 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00076102
Status:
COMPLETED
Last Update Posted:
2018-04-23
First Post:
2004-01-13
Brief Title:
Pirfenidone in Children and Young Adults With Neurofibromatosis Type I and Progressive Plexiform Neurofibromas
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Phase II Trial of Pirfenidone in Children Adolescents and Young Adults With Neurofibromatosis Type 1 and Progressive Plexiform Neurofibromas
Status:
COMPLETED
Status Verified Date:
2018-04
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:
Background
Neurofibromatosis Type 1 NF1 is an autosomal dominant progressive genetic disorder characterized by diverse clinical manifestations Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas which are benign nerve sheath tumors that may cause severe morbidity and possible mortality The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability Gene profile analysis demonstrates overexpression of fibroblast growth factor epidermal growth factor and platelet-derived growth factor in plexiform neurofibromas in patients with NF1 Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed and has established the phase II dose the dose resulting in a mean drug exposure AUC not more than 1 standard deviation below the mean drug exposure AUC in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions Pirfenidone has been well tolerated
Objectives
To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas
To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas
To describe and define the toxicities of pirfenidone
Eligibility
Individuals greater than or equal to 3 years to less than or equal to 21 years of age with a clinical diagnosis of NF1 and inoperable measurable and progressive plexiform neurofibromas that have the potential to cause substantial morbidity
Design
The phase II dose will be used in a single stage single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown For this reason time to disease progression on the placebo arm of an ongoing National Cancer Institute NCI Pediatric Oncology Branch POB placebo-controlled double-blind cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas
Funding source - Food and Drug Administration FDA Office of Orphan Products Development OOPD
Neurofibromatosis Type 1 NF1 is an autosomal dominant progressive genetic disorder characterized by diverse clinical manifestations Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas which are benign nerve sheath tumors that may cause severe morbidity and possible mortality The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability Gene profile analysis demonstrates overexpression of fibroblast growth factor epidermal growth factor and platelet-derived growth factor in plexiform neurofibromas in patients with NF1 Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed and has established the phase II dose the dose resulting in a mean drug exposure AUC not more than 1 standard deviation below the mean drug exposure AUC in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions Pirfenidone has been well tolerated
Objectives
To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas
To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas
To describe and define the toxicities of pirfenidone
Eligibility
Individuals greater than or equal to 3 years to less than or equal to 21 years of age with a clinical diagnosis of NF1 and inoperable measurable and progressive plexiform neurofibromas that have the potential to cause substantial morbidity
Design
The phase II dose will be used in a single stage single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown For this reason time to disease progression on the placebo arm of an ongoing National Cancer Institute NCI Pediatric Oncology Branch POB placebo-controlled double-blind cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas
Funding source - Food and Drug Administration FDA Office of Orphan Products Development OOPD
Detailed Description:
Background
Neurofibromatosis Type 1 NF1 is an autosomal dominant progressive genetic disorder characterized by diverse clinical manifestations Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas which are benign nerve sheath tumors that may cause severe morbidity and possible mortality The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability Gene profile analysis demonstrates overexpression of fibroblast growth factor epidermal growth factor and platelet-derived growth factor in plexiform neurofibromas in patients with NF1 Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed and has established the phase II dose the dose resulting in a mean drug exposure AUC not more than 1 standard deviation below the mean drug exposure AUC in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions Pirfenidone has been well tolerated
Objectives
To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas
To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas
To describe and define the toxicities of pirfenidone
Eligibility
Individuals greater than or equal to 3 years to less than or equal to 21 years of age with a clinical diagnosis of NF1 and inoperable measurable and progressive plexiform neurofibromas that have the potential to cause substantial morbidity
Design
The phase II dose will be used in a single stage single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown For this reason time to disease progression on the placebo arm of an ongoing National Cancer Institute NCI Pediatric Oncology Branch POB placebo-controlled double-blind cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas will be used as historical control to determine if pirfenidone increases time to disease progression Eligibility criteria and method of tumor measurements are identical for both trials
Pirfenidone will be administered orally as capsules at a dose of 500 mgm2 three times a day q8h for cycles of 28 days with no rest period between cycles based on the results of our pediatric phase I trial
Neurofibromatosis Type 1 NF1 is an autosomal dominant progressive genetic disorder characterized by diverse clinical manifestations Patients with NF1 have an increased risk of developing tumors of the central and peripheral nervous system including plexiform neurofibromas which are benign nerve sheath tumors that may cause severe morbidity and possible mortality The histopathology of these tumors suggests that events connected with formation of fibroblasts might constitute a point of molecular vulnerability Gene profile analysis demonstrates overexpression of fibroblast growth factor epidermal growth factor and platelet-derived growth factor in plexiform neurofibromas in patients with NF1 Pirfenidone is a novel antifibrotic agent that inhibits these and other growth factors Clinical experience in adults has demonstrated that pirfenidone is effective in a variety of fibrosing conditions and pirfenidone is presently under study in a phase II trial for adults with progressive plexiform neurofibromas A phase I trial of pirfenidone in children and young adults with NF1 and plexiform neurofibromas was completed and has established the phase II dose the dose resulting in a mean drug exposure AUC not more than 1 standard deviation below the mean drug exposure AUC in adults who received pirfenidone at the dose level demonstrating activity in fibrosing conditions Pirfenidone has been well tolerated
Objectives
To determine whether pirfenidone increases the time to disease progression based on volumetric measurements in children and young adults with NF1 and growing plexiform neurofibromas
To define the objective response rate to pirfenidone in NF1-related plexiform neurofibromas
To describe and define the toxicities of pirfenidone
Eligibility
Individuals greater than or equal to 3 years to less than or equal to 21 years of age with a clinical diagnosis of NF1 and inoperable measurable and progressive plexiform neurofibromas that have the potential to cause substantial morbidity
Design
The phase II dose will be used in a single stage single arm phase II trial The natural history of the growth of plexiform neurofibromas is unknown For this reason time to disease progression on the placebo arm of an ongoing National Cancer Institute NCI Pediatric Oncology Branch POB placebo-controlled double-blind cross-over phase II trial of the farnesyltransferase inhibitor R115777 for children and young adults with NF1 and progressive plexiform neurofibromas will be used as historical control to determine if pirfenidone increases time to disease progression Eligibility criteria and method of tumor measurements are identical for both trials
Pirfenidone will be administered orally as capsules at a dose of 500 mgm2 three times a day q8h for cycles of 28 days with no rest period between cycles based on the results of our 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?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| FD-R-0002128 | OTHER_GRANT | FDA OOPD | None |
| 04-C-0080 | None | None | None |