Phase II Trial of Vandetanib (ZD6474, Caprelsa(R) in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Number of Participants With a Clinical Activity-radiographic Response
研究概览
简要总结
Background:
-Some people with wild-type gastrointestinal stromal tumors (WT-GIST) have a deficiency in one of their proteins called succinate dehydrogenase (SDH). Vandetanib is a cancer drug that has been approved to treat thyroid cancer and has been used with some success in other tumors that have a similar loss of SDH. Researchers want to see if this drug can also decrease tumor growth in people with WT-GIST.
Objectives:
-To test whether the study drug will benefit people with WT-GIST.
Eligibility:
-Adults and children 3 years old and older with WT-GIST.
Design:
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Researchers will test participants tumor tissue to confirm it is the wild type of GIST.
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Participants will be screened with a medical history, physical exam, and blood tests. They will also have electrical recording of the heart (Eastern Cooperative Oncology Group (ECOG)) and scans of the tumor.
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Participants will take the study drug in 28-day cycles. Their doctor will decide how many cycles they can complete.
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They will take the study drug once every day and record it in a diary.
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On Day 14, they will also visit their doctor to look for side effects.
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Before cycles 2, 3 and 4, participants will have a physical exam, urine tests, blood pressure check, and blood tests. These tests will then be done periodically for as long as they are in the study.
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Before cycle 4, scans will be done to check the size of the cancer. Most of these will be repeated every 3-6 cycles.
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When they stop taking the study drug, participants will return to the clinic for a physical exam and blood tests.
详细描述
Background:
- Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, resistant to cytotoxic chemotherapy and radiation therapy. KIT and platelet derived growth factor receptor alpha (PDGFRA) mutations have been identified as tumor initiating events in 85% of adult patients with GIST, but 85% of GISTs in pediatric patients lack KIT and PDGFRA mutations (wild-type) and imatinib is not as effective in eliciting objective responses.
- Recent work in the Pediatric and Wild-Type (wt) GIST Clinic at the National Cancer Institute (NCI) led to the identification of succinate dehydrogenase (SDH) germline mutations in 12% patients with wt-GIST (6/34). SDH protein expression evaluated using immunohistochemistry (IHC) was markedly decreased or absent in 18/18 patients with pediatric wt-GIST. Thus the majority of wt-GIST are SDH-deficient. Vandetanib (ZACTIMA; ZD6474; AstraZeneca) is an oral small molecule antineoplastic drug that inhibits vascular endothelial growth factor receptor 2 (VEGFR2), estimated glomerular filtration rate (EGFR), and rearranged during transfection (RET)-dependent signaling. Preliminary preclinical data demonstrate marked growth inhibition of SDH-mutant/deficient renal cell carcinoma cell lines when treated with vandetanib.
Objective(s):
-Primary: To assess the clinical activity (radiographic response Response Evaluation Criteria in Solid Tumors (RECIST v1.1) of vandetanib in children and adults with wt-GIST using RECIST (v1.1).
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
Vandetanib in Children
Children with measurable localized or metastatic wt-GIST
干预措施: Vandetanib (Drug)
Vandetanib in Adults
Adults with measurable localized or metastatic wt-GIST
干预措施: Vandetanib (Drug)
结局指标
主要结局
Number of Participants With a Clinical Activity-radiographic Response
时间窗: Every 3 cycles x4 and then every 6 cycles (1 cycle = 28 days) until removal from protocol therapy, an average of 12 months.
Clinical activity will be assessed primarily by radiographic response of measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease is neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum diameters while on study.
次要结局
- Percentage of Participants Overall Survival(Overall survival was computed using the number of months from the date of on study to the date of death, an average of 12 months.)
- Count of Participants With Serious and Non-serious Adverse Events(Date treatment consent signed to date off study, approximately 32 months and 1 day.)
- Progression Free-Survival(Patients will be evaluated approximately 60 days after last dose of investigational drug until removal of protocol therapy, an average of 12 months.)
- Maximum Standardized Uptake Value (SUVmax) on Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)(Baseline and at a subsequent PET performed on or about day 3-6 of cycle 1)
研究者
Brigitte Widemann, M.D.
Principal Investigator
National Cancer Institute (NCI)