Phase I Study of Nilotinib Given With Radiation For Patients With High Risk Chordoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD).
研究概览
简要总结
The study drug, Nilotinib, is believed to slow down tumor growth by regulating a gene involved in cellular growth of chordoma cells. During this research study, subjects will also receive radiation therapy which is considered a standard treatment for advanced chordomas. It is hoped by adding nilotinib, the benefits of radiation therapy can be enhanced without adding significant toxicities.
The purpose of this research study is to determine the safety of nilotinib when used in combination with radiation therapy, and the highest dose of nilotinib that can be given safely with radiation therapy.
详细描述
Nilotinib will be taken orally daily in two cycles of 28 days each. Two weeks after taking nilotinib, subjects will begin radiation therapy. Radiation therapy will continue every weekday until Day 56 of the study. If it is determined that the subject's tumor cannot be removed by surgery, an additional 3 weeks of radiation therapy will be applied after Day 56 of the study.
During study visits subjects will have physical exams, routine blood tests, urine and blood clotting tests, and EKGs. Subjects will also have tumor assessment by chest CT and MRI or CT of the tumor at screening, on approximately Day 56 of the study, then every 6 months for one year and then annually thereafter if ther is no disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed chordoma
- •Considered to have high risk disease
- •Measurable disease
- •Life expectancy > 3 months
- •Adequate organ function
- •Able to swallow oral capsules
排除标准
- •Previous treatment with any other tyrosine kinase inhibitor
- •Previous treatment with radiotherapy to the primary or recurrent chordomas
- •Impaired cardiac function
- •Currently receiving treatment with strong CYP3A4 inhibitors
- •Requires anticoagulation with coumadin
- •Impaired GI function or GI disease that may significantly alter the absorption of study drug
- •Acute or chronic pancreatic disease
- •Known cytopathologically confirmed CNS infiltration
- •Another primary malignant disease which requires systemic treatment
- •Acute or chronic liver disease or severe renal disease considered unrelated to the cancer
- •History of significant congenital or acquired bleeding disorder unrelated to cancer
- •Major surgery within 4 weeks prior to Day 1 of the study or who have not recovered from prior surgery
- •Treatment with other investigational agents within 30 days of Day 1
- •History of non-compliance to medical regimens
- •Pregnant or breast-feeding
研究组 & 干预措施
Nilotinib/XRT
Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily radiation therapy until completion of radiation therapy. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.
干预措施: Nilotinib (Drug)
Nilotinib/XRT
Nilotinib is administered 400mg PO BID for 2 weeks and then administered concurrently with daily radiation therapy until completion of radiation therapy. Participants can then undergo surgery if clinically possible. After either surgery or definitive radiation, participants have the option to continue on nilotinib therapy.
干预措施: Radiation therapy (Radiation)
结局指标
主要结局
To determine the dose limiting toxicities (DLTs) for participants when treated above the maximum tolerated dose (MTD).
时间窗: 2 years
A DLT will be defined as any of the following events occurring during days 1-56 of study according to CTCAE version 4.0. MTD is then determined by identifying a dose cohort demonstrating \> or = 30% rate of DLTs, which are defined as: * Any Grade ≥ 3 nonhematologic toxicity except alopecia, nausea, or vomiting not otherwise controlled by maximual supportive care. * Grade 4 neutropenia (ANC \< 500/µL) lasting \> 5 days, Grade 3 thrombocytopenia lasting \> 7 days, or Grade 4 thrombocytopenia * Failure to resume treatment delays within a defined period of time.
次要结局
- Number of Participants with Adverse Events(2 years)
- Survival(2 years)
- PDGFR signaling(2 years)
研究者
Edwin Choy, MD
Instructor
Massachusetts General Hospital