Ignite Creation Date:
2025-12-24 @ 7:43 PM
Ignite Modification Date:
2025-12-29 @ 9:23 AM
Study NCT ID:
NCT01362803
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-08
First Post:
2011-05-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
AZD6244 Hydrogen Sulfate for Children With Nervous System Tumors
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
A Phase I/II Study of the Mitogen Activated Protein Kinase (MEK) 1 Inhibitor Selumetinib (AZD6244; Hydrogen Sulfate in Children With Neurofibromatosis Type 1 (NF1) and Inoperable Plexiform Neurofibromas (PN)
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-10-08
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:
\- Plexiform neurofibromas are tumors that grow in and around nerves. The only way to treat them is with surgery. Some of these tumors cannot be completely removed. The tumors may be too large, too numerous, or in a bad location for surgery. An experimental drug called AZD6244 hydrogen sulfate may be able to prevent the tumors from growing, slow down their growth, or shrink them. This drug has been tested in adults with cancer and in children with some types of brain cancer. This study will test how well this drug works with these types of tumors.
Objectives:
\- To study the safety and effectiveness of AZD6244 hydrogen sulfate in children and young adults with plexiform neurofibromas that cannot be completely removed by surgery.
Eligibility:
\- Children and young adults between 12 and 18 years of age who have plexiform neurofibromas that cannot be completely removed by surgery.
Design:
* Patients will be screened with a physical exam, medical history, blood tests, and imaging studies.
* They will take the study drug twice a day with 8 ounces of water, every day for 28-day cycles of treatment. During study visits, participants will have blood and urine tests and physical exams. They will also have imaging studies to examine the tumor sizes and locations. They will answer questions about their health. They may have other tests as needed.
* Participants will continue to receive the study drug as long as they have no severe side effects and the disease is not getting worse.
\- Plexiform neurofibromas are tumors that grow in and around nerves. The only way to treat them is with surgery. Some of these tumors cannot be completely removed. The tumors may be too large, too numerous, or in a bad location for surgery. An experimental drug called AZD6244 hydrogen sulfate may be able to prevent the tumors from growing, slow down their growth, or shrink them. This drug has been tested in adults with cancer and in children with some types of brain cancer. This study will test how well this drug works with these types of tumors.
Objectives:
\- To study the safety and effectiveness of AZD6244 hydrogen sulfate in children and young adults with plexiform neurofibromas that cannot be completely removed by surgery.
Eligibility:
\- Children and young adults between 12 and 18 years of age who have plexiform neurofibromas that cannot be completely removed by surgery.
Design:
* Patients will be screened with a physical exam, medical history, blood tests, and imaging studies.
* They will take the study drug twice a day with 8 ounces of water, every day for 28-day cycles of treatment. During study visits, participants will have blood and urine tests and physical exams. They will also have imaging studies to examine the tumor sizes and locations. They will answer questions about their health. They may have other tests as needed.
* Participants will continue to receive the study drug as long as they have no severe side effects and the disease is not getting worse.
Detailed Description:
Background
* Patients with Neurofibromatosis 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. PN may be congenital and appear to have the fastest growth rate in young children. Surgery is the only standard treatment option available for PN. However, this is often difficult due to the encasement of vital structures, and extensive and invasive PN growth.
* PN are composed of neoplastic Schwann cells that lack NF1 gene expression. This results in upregulation of Ras, which initiates several signaling cascades regulating cell proliferation.
* Selumetinib (AZD6244 hyd sulfate), a novel orally bioavailable mitogen activated protein kinase inhibitor, is a specific inhibitor of MEK 1, which may mediate anti-tumor effects in PN by inhibition of downstream signaling of Ras. Selumetinib is currently undergoing evaluation in adult cancers and children with brain tumors.
* In this phase I study of selumetinib directed at NF1 PN, we have observed a degree of activity which has not been observed previously; therefore a phase II evaluation will be conducted.
Objectives
Phase I:
* To determine the maximum tolerated dose (MTD) of oral selumetinib administered daily to pediatric patients with NF1 and inoperable PN. Based on the results of the dose escalation in this study, the current MTD has been determined as 20 mg/m2/dose. To be consistent in pediatric dosing, an additional dose level of 25 mg/m2/dose was added, which is the MTD recently determined in a study conducted by the Pediatric Brain Tumor Consortium (PBTC). Amendment H (November 2014): The MTD has been determined to be 25 mg/m\^2/dose.
* To define the acute and chronic toxicities and pharmacokinetics (PK) of selumetinib. Completed with amendment H.
Phase II:
-Primary objectives: To evaluate the confirmed partial and complete response rate of selumetinib using volumetric MRI analysis in children and young adults with NF1 and inoperable PN with PN related morbidity at the time of enrollment.
Eligibility
Pediatric Patients (\>= 2 and \<=18 years) who are able to swallow intact capsules, with NF1 and inoperable measurable PN that cause or have the potential to cause significant morbidity.
Design
* Selumetinib will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment cycle). In the phase I portion, limited dose escalations will be performed to define the MTD based on tolerability of selumetinib during the first three treatment cycles. In the phase II portion, the recommended phase II dose level (RP2D) will be administered.
* Phase II: Patients will be enrolled on one of two strata:
* Stratum 1: PN related morbidity present at enrollment
---PN related pain, disfigurement, or difficulty in physical functioning
* Stratum 2: No significant PN related morbidity present at enrollment, but potential for development of PN morbidity
* Patient reported and functional outcomes will be evaluated at regular intervals.
* Disease status will be evaluated using volumetric MRI analysis at regular intervals.
* The day 1 and steady state plasma PK and PD of selumetinib will be evaluated.
* Patients with Neurofibromatosis 1 (NF1) have an increased risk of developing tumors of the central and peripheral nervous system, including plexiform neurofibromas (PN), which are benign nerve sheath tumors that are among the most debilitating complications of NF1. PN may be congenital and appear to have the fastest growth rate in young children. Surgery is the only standard treatment option available for PN. However, this is often difficult due to the encasement of vital structures, and extensive and invasive PN growth.
* PN are composed of neoplastic Schwann cells that lack NF1 gene expression. This results in upregulation of Ras, which initiates several signaling cascades regulating cell proliferation.
* Selumetinib (AZD6244 hyd sulfate), a novel orally bioavailable mitogen activated protein kinase inhibitor, is a specific inhibitor of MEK 1, which may mediate anti-tumor effects in PN by inhibition of downstream signaling of Ras. Selumetinib is currently undergoing evaluation in adult cancers and children with brain tumors.
* In this phase I study of selumetinib directed at NF1 PN, we have observed a degree of activity which has not been observed previously; therefore a phase II evaluation will be conducted.
Objectives
Phase I:
* To determine the maximum tolerated dose (MTD) of oral selumetinib administered daily to pediatric patients with NF1 and inoperable PN. Based on the results of the dose escalation in this study, the current MTD has been determined as 20 mg/m2/dose. To be consistent in pediatric dosing, an additional dose level of 25 mg/m2/dose was added, which is the MTD recently determined in a study conducted by the Pediatric Brain Tumor Consortium (PBTC). Amendment H (November 2014): The MTD has been determined to be 25 mg/m\^2/dose.
* To define the acute and chronic toxicities and pharmacokinetics (PK) of selumetinib. Completed with amendment H.
Phase II:
-Primary objectives: To evaluate the confirmed partial and complete response rate of selumetinib using volumetric MRI analysis in children and young adults with NF1 and inoperable PN with PN related morbidity at the time of enrollment.
Eligibility
Pediatric Patients (\>= 2 and \<=18 years) who are able to swallow intact capsules, with NF1 and inoperable measurable PN that cause or have the potential to cause significant morbidity.
Design
* Selumetinib will be administered orally BID on a continuous dosing schedule (28 days = 1 treatment cycle). In the phase I portion, limited dose escalations will be performed to define the MTD based on tolerability of selumetinib during the first three treatment cycles. In the phase II portion, the recommended phase II dose level (RP2D) will be administered.
* Phase II: Patients will be enrolled on one of two strata:
* Stratum 1: PN related morbidity present at enrollment
---PN related pain, disfigurement, or difficulty in physical functioning
* Stratum 2: No significant PN related morbidity present at enrollment, but potential for development of PN morbidity
* Patient reported and functional outcomes will be evaluated at regular intervals.
* Disease status will be evaluated using volumetric MRI analysis at regular intervals.
* The day 1 and steady state plasma PK and PD of selumetinib will be evaluated.
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?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 11-C-0161 | None | None | View |