Y-90 Alone or With Sorafenib for Pre-Transplant Hepatocellular Carcinoma
2016年9月13日 更新者：Laura Kulik、Northwestern University
A Single-Center Proof of Concept Pilot Study to Evaluate the Safety, Efficacy, and Tolerability of Sorafenib Combined With Therasphere in Subjects With Hepatocellular Carcinoma Awaiting Liver Transplantation.
A research study to determine the safety, efficacy, and tolerability of Therasphere® (also known as Y-90, or Y-90 Therasphere) combined with or without sorafenib (Nexavar®), in patients with hepatocellular carcinoma (HCC, or liver cancer), awaiting liver transplantation.
研究概览
详细说明
Because Hepatocellular carcinoma (HCC) grows by forming new blood vessels liver transplant (OLT) offers the best chance for long term survival.
However, with the growing number of patients who require OLT, prolonged wait list times often lead to drop out from the transplant list due to tumor progression.
Some patients are granted an "upgrade",within the generally accepted guidelines for transplant eligibility, in order to expedite the access of patients with early HCC to transplantation before tumor progression.
The use of therapies like radioembolization also known as Yttrium-90 ([Y-90] a procedure where very small beads coated with radiation are injected directly into the tumor through an artery in your groin) while awaiting OLT has become common at most transplant centers, including Northwestern, to help patients reach transplant.
Additionally, these treatments are being used to move patients to a status eligible for transplant.
We are studying whether a combination approach with systemic therapy and therapy applied directly to the liver, will be more successful than a single therapy .
Angiogenesis (a process involving the growth of new blood vessels from pre-existing vessels) plays an important role in the early stages of HCC.
A decrease in angiogenesis both locally within the treated tumor as well as in any existing tumor cells, not yet detected, would hopefully decrease the incidence of post transplant recurrence of HCC.
All subjects enrolled in this study will be treated with the use of Therasphere, Y-90, which is composed of nonbiodegradable glass microspheres coated with the radioactive compound Y-90 which are injected into the hepatic artery.
The concentrated radioactive microspheres within the tumor lead to "inside-out" radiation.
Half of the subjects will be treated with sorafenib (NEXAVAR®) in conjunction with Y-90.
The determination of which subjects will receive sorafenib will be made randomly, like the flip of a coin.
Sorafenib works by slowing the growth of the tumor cell , attacking the tumor from the outside.
Researchers hope to determine whether the subjects treated with sorafenib have an overall improved response to liver directed therapy with Y-90 Therasphere.
研究类型
介入性
注册 (实际的)
24
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern Memorial Hospital
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Adult > 18 years olf of either gender
- Diagnosis of HCC confirmed by biopsy, CT, or MRI
- Able to carry out activities of daily living, awake >50% of waking hours
- Meets eligibility for liver transplantation
- No prior treatment for HCC
- Ability to understand and sign the informed consent
- Child-bearing women and any men agree to use two forms of birth control (one of which should be a barrier method) during the course of therapy and for 8 weeks afterward.
Exclusion Criteria:
- Less than or = 18 years old
- Ineligible for transplant due to comorbid disease
- Renal Failure requiring dialysis of any kind
- Severe Cardiac disease
- History of a stroke
- Evidence of metastatic disease- or tumors that have spread outside the liver
- Known human immunodeficiency virus (HIV) infection
- Uncontrolled blood pressure (systolic > 160) despite medication(s)
- Major surgery within 4 weeks prior to the screening visit
- Active clinically serious infection
- Serious non-healing wound, ulcer, or bone fracture.
- History of gastrointestinal bleeding (GIB) within 6 weeks prior to the screening visit
- Prior transplant of any kind
- Must be able to swallow oral pills, tablets or capsules of any size
- Use of St. John's Wort or rifampin (rifampicin).
- Currently being treated with Interferon and/or Ribavirin therapy due to the thrombocytopenias, lymphopenias and anemias observed with use of these two medications.
- Known or suspected allergy to sorafenib or any agent given in the course of this trial.
- Any malabsorption problem
- Pregnancy or lactation. Women of childbearing potential must have a negative pregnancy test 7 days prior to beginning therapy.
- No potential living donor transplant (LDT-donor identified and worked up by the time of randomization into this study. If a living donor is later identified- the subject will be allowed to continue in the study. Sorafenib will be stopped at a minimum of 7 days prior to transplant surgery.
- Active alcohol use, drug use, or a psychiatric disease that would, in the opinion of the PI or a subinvestigator (sub-I), prevent the subject from complying with the study protocol and/or endanger the subject during their participation in the study
- Inability of the potential subject to read, understand and sign the informed consent document
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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有源比较器：A: Y-90 alone
Patients randomized to Arm A will proceed to Y-90 treatment alone in the Northwestern standard of care procedure
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Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion
其他名称：
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实验性的：B: Sorafenib + Y-90
Patients randomized to Arm B will start sorafenib at a dose of 400 mg twice daily for bilirubin ≤ 1.5 x ULN and 200 mg twice daily for bilirubin > 1.5 x ULN to ≤ 3 x ULN.
After 14 days of sorafenib therapy (+/- 3 days) patients will proceed to Y-90 in the Northwestern standard of care procedure
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Patients undergo radioembolization with Yttrium 90 microspheres by hepatic artery infusion
其他名称：
Randomized to Y-90 ± Sorafenib
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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To Evaluate sorafenib as an adjunct to Y-90 for control of HCC as a bridge/downstage to transplant
大体时间：Up to one year
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Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90.
They have imaging (CT/MRI) 2 weeks after starting Sorafenib then are treated.
Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant.
Repeat imaging is done at 4 weeks, and then every 3 months post-treatment.
Subjects not receiving Sorafenib are treated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.
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Up to one year
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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To characterize the toxicity profile of sorafenib and Y90 using NCI CTC toxicity grading scales.
大体时间：up to 1 year
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Subjects randomized to receive Sorafenib take the drug for 2 weeks before treatment with Y90.
They have imaging (CT/MRI) 2 weeks after starting Sorafenib then are treated.
Post-treatment patients have blood drawn and adverse event evaluation at 2 weeks, 4 weeks, 6 weeks, and then every 6 weeks up to 1 year or time of transplant.
Repeat imaging is done at 4 weeks, and then every 3 months post-treatment.
Subjects not receiving Sorafenib are treated with Y90 and then are evaluated post-treatment the same as the subjects that receive the drug.
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up to 1 year
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To identify predictive and prognostic markers of how the liver cancer will respond to treatment.
大体时间：up to 1 year
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All subjects are evaluated with lab work and adverse event assessment at 2, 4, and 6 weeks post-treatment, and then every 6 weeks up to 1 year or when they receive transplant.
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up to 1 year
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Laura Kulik, MD、Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation
- 首席研究员：Riad Salem, MD、Northwestern University, Northwestern Memorial Hospital, Northwestern Medical Faculty Foundation
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Kulik L, Vouche M, Koppe S, Lewandowski RJ, Mulcahy MF, Ganger D, Habib A, Karp J, Al-Saden P, Lacouture M, Cotliar J, Abecassis M, Baker T, Salem R. Prospective randomized pilot study of Y90+/-sorafenib as bridge to transplantation in hepatocellular carcinoma. J Hepatol. 2014 Aug;61(2):309-17. doi: 10.1016/j.jhep.2014.03.023. Epub 2014 Mar 27.
- Vouche M, Kulik L, Atassi R, Memon K, Hickey R, Ganger D, Miller FH, Yaghmai V, Abecassis M, Baker T, Mulcahy M, Nayar R, Lewandowski RJ, Salem R. Radiological-pathological analysis of WHO, RECIST, EASL, mRECIST and DWI: Imaging analysis from a prospective randomized trial of Y90 +/- sorafenib. Hepatology. 2013 Nov;58(5):1655-66. doi: 10.1002/hep.26487. Epub 2013 Oct 1.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2009年2月1日
初级完成 (实际的)
2015年7月1日
研究完成 (实际的)
2016年9月1日
研究注册日期
首次提交
2009年2月16日
首先提交符合 QC 标准的
2009年2月17日
首次发布 (估计)
2009年2月18日
研究记录更新
最后更新发布 (估计)
2016年9月15日
上次提交的符合 QC 标准的更新
2016年9月13日
最后验证
2016年9月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.