Clinical Trial: A Phase II Trial of the Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Stromal Tumors (GIST)
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Phase II Trial of the Mitogen Activated Protein Kinase Kinase (MEK1/2) Inhibitor Selumetinib (AZD6244 Hydrogen Sulfate) in Patients With Neurofibromatosis Type 1 (NF1) Mutated Gastrointestinal Strom
Brief Summary:
BACKGROUND:
- Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, and traditional cytotoxic chemotherapy is not effective. Patients with Neurofibromatosis 1 (NF1) have an increased risk of developing GIST, and surgery remains the only standard treatment option for NF1-related GIST. While the tyrosine kinase inhibitors (TKIs) imatinib and sunitinib prolong survival in patients with KIT/PDGFRA mutated GIST, they have no documented efficacy in patients with NF1 related GISTs, which lack KIT/PDGFRA mutations. Radiation therapy also seems to be ineffective. Therefore, new therapies are needed.
- Selumetinib (AZD6244 hyd sulfate), a novel orally bioavailable mitogen activated protein kinase inhibitor, is a specific inhibitor of MEK 1/2, which is currently undergoing evaluation in adults with refractory cancers, in adults and children with NF1 and plexiform neurofibromas (PN) and children with brain tumors. Evaluation of selumetinib in children and young adults with NF1 related plexiform neurofibromas (PN) has demonstrated activity with most patients demonstrating some PN shrinkage, and a partial response rate of 71%. Selumetinib has also demonstrated activity in children with NF1 and low-grade gliomas. It is thus possible that selumetinib may mediate anti-tumor effects in NF1 GIST by inhibition of downstream signaling of Ras.
OBJECTIVES:
- To estimate the response rate of selumetinib in children and adults with measurable NF1-mutated GIST which is unresectable, progressive or metastatic.
ELIGIBILITY:
- Patients who are greater
Detailed Summary:
BACKGROUND:
- Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract, and traditional cytotoxic chemotherapy is not effective. Patients with Neurofibromatosis 1 (NF1) have an increased risk of developing GIST, and surgery remains the only standard treatment option for NF1-related GIST. While the tyrosine kinase inhibitors (TKIs) imatinib and sunitinib prolong survival in patients with KIT/PDGFRA mutated GIST, they have no documented efficacy in patients with NF1 related GISTs, which lack KIT/PDGFRA mutations. Radiation therapy also seems to be ineffective. Therefore, new therapies are needed.
- Selumetinib (AZD6244 hyd sulfate), a novel orally bioavailable mitogen activated protein kinase inhibitor, is a specific inhibitor of MEK 1/2, which is currently undergoing evaluation in adults with refractory cancers, in adults and children with NF1 and plexiform neurofibromas (PN) and children with brain tumors. Evaluation of selumetinib in children and young adults with NF1 related plexiform neurofibromas (PN) has demonstrated activity with most patients demonstrating some PN shrinkage, and a partial response rate of 71%. Selumetinib has also demonstrated activity in children with NF1 and low-grade gliomas. It is thus possible that selumetinib may mediate anti-tumor effects in NF1 GIST by inhibition of downstream signaling of Ras.
OBJECTIVES:
- To estimate the response rate (radiologic response as defined by RECIST v1.1) of selumetinib in children and adults with measurable NF1-mutated GIST which is unresectable, progressive or metastatic.
ELIGIBILITY:
-
Sponsor: National Cancer Institute (NCI)
- To describe the toxicities of selumetinib in patients with NF1- mutated GIST. [ Time Frame: End of treament ]
- To estimate the progression-free survival (PFS). [ Time Frame: Time of progression ]
- To perform a descriptive comparison of the response rate by CT-based imaging criteria developed by Choi compared to response rate as defined by RECIST. [ Time Frame: End of treatment ]
Current Primary Outcome: To estimate the response rate (radiologic response RECIST v1.1) of selumetinib in children and adults with NF1-mutated measurable gastrointestinal stromal tumor (GIST). [ Time Frame: End of treatment ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
Original Secondary Outcome: Same as current
Information By: National Institutes of Health Clinical Center (CC)
Dates:
Date Received: April 11, 2017
Date Started: April 6, 2017
Date Completion: February 1, 2023
Last Updated: April 12, 2017
Last Verified: April 11, 2017
