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)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Efficacy
研究概览
简要总结
Background:
Gastrointestinal stromal tumors (GIST) can cause serious medical problems. The only known treatment is surgery. But completely removing a GIST tumor with surgery is often not possible. Researchers want to see if a new drug, selumetinib, can help treat these tumors.
Objective:
To find out if selumetinib shrinks or slows the growth of GIST tumors and to see its side effects.
Eligibility:
People ages 3 and over who have one or more GIST tumors and may have neurofibromatosis type I (also called NF1). Their NF1 GIST has shown some growth or cannot be completely removed with surgery.
Design:
Participants will be screened with heart and eye tests and scans.
Participants will be told what foods and medicines they cannot take during the study. Participants will keep a diary of the medicine they take during the study.
Participants will take selumetinib capsules twice daily on an empty stomach for 28 days in a row. This is 1 cycle.
During the cycles, participants will have study visits. These may include:
Medical history
Physical exam
Blood and urine tests
Heart tests
Scans of their tumors
Eye exam
Positron emission tomography scan. They will be get radioactive glucose an IV line. They will lie quietly in a darkened room for 50-60 minutes then have the scan.
Participants will answer questions about how they are feeling.
Participants can stay in the study until they have bad side effects or their tumor grows.
After finishing treatment, participants will be watched for side effects for 30 days.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 1
Patients > 18 years of age
干预措施: Selumetinib (AZD6244 hyd sulfate) 50mg/dose (Drug)
Arm 2
Patients < 18 years of age
干预措施: Selumetinib (AZD6244 hyd sulfate) 25mg/m2 (Drug)
结局指标
主要结局
Efficacy
时间窗: End of treatment
Estimate the response rate (radiologic response RECIST v1.1) of selumetinib in children and adults with NF1- mutated measurable gastrointestinal stromal tumor (GIST).
次要结局
未报告次要终点