Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors
A Phase I Dose-Escalation Trial of Oral Hydroxychloroquine Plus Oral Sorafenib to Treat Patients With Refractory or Relapsed Solid Tumors
Patients with recurrent, refractory or metastatic solid tumors have a dismal prognosis with few viable treatment options. Hydroxychloroquine (HCQ) is an agent that has been widely used to treat malaria. Because HCQ also inhibits autophagy, a process central to survival of cancer in the face of metabolic stress, including the effects of anti-cancer therapy, it is now in human cancer trials combined with other agents to attempt to boost the efficacy of those agents. Autophagy inhibition improves the activity of sorafenib in hepatocellular carcinoma.
Sorafenib is an oral multi-kinase inhibitor that blocks not only receptor tyrosine kinases such as KIT, VEGFR and PDGFR but also serine/threonine kinases along the RAS/RAF/MEK/ERK pathway.
The investigators propose to treat patients with refractory or relapsed solid tumors with sorafenib, to boost its efficacy while attempting to mitigate its toxicity by combining with HCQ.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Texas
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San Antonio、Texas、美国、78229
- Cancer Therapy and Research Center at UTHSCSA
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Able to provide informed consent
- Not on immune-modulating drugs, except those used as study drug premedication, unless the principal investigator grants an exception (which exception must be documented in writing)
- Patients with relapsed or refractory solid tumors with no viable treatment options
- Measurable disease within 30 days of study enrollment
- Blood hemoglobin > 8.5 gm/dl within 7 days of study enrollment
- Absolute neutrophil count > 1000/mm3 within 7 days of study enrollment
- Platelet count > 50,000/mm3 within 7 days of study enrollment
- SGOT <10x upper limit of normal within 7 days of study enrollment
- No chemotherapy or radiation therapy in the 14 days prior to initiation of treatment on this study. No other concurrent chemotherapy, surgery or radiation therapy during this protocol except surgery or radiation therapy to control symptoms with concurrence of the principal investigator.
- No contraindication to any study treatment
- No active major medical problems, including untreated or uncontrolled infections
- If of reproductive potential, a negative urine or blood pregnancy test within 3 days of study enrollment, and agreement to use adequate contraception. In relevant subjects, pregnancy testing will continue monthly while on treatment unless the subject is no longer able to become pregnant or there is sufficient justification otherwise
- Not breast feeding
- Life expectancy > 6 months
- ECOG performance status < 2
- Age 18+ years
- No active substance abuse in the prior 6 months
- Not on digoxin or cimetidine
Exclusion Criteria:
- Contraindication or hypersensitivity to any study drug or its components or excipients
- Current pregnancy or breast feeding
- Inability to document adequate contraception if a female of reproductive potential
- Chemotherapy or radiation therapy within the 14 days prior to initiation of study treatment
- Prior treatment with sorafenib. Prior HCQ use is not an exclusion.
- Life expectancy < 6 months
- ECOG performance status > 2
- Symptomatic coronary artery disease (including uncontrolled angina, congestive heart failure, and the like)
- Uncontrolled hypertension (diastolic BP consistently >100 mm Hg or systolic BP consistently >160 mm Hg on a regular basis)
- Uncontrolled, symptomatic cardiac arrhythmia
- Active substance abuse in the prior 6 months
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 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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实验性的:Sorafenib plus Hydroxychloroquine
Dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD. Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle. Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2. |
dose escalation of sorafenib combined with hydroxychloroquine (HCQ) to a maximum of sorafenib 400 mg PO BID plus HCQ 400 mg PO QD. Drugs are given on an intermittent schedule of days 1-5/week in a 28-day cycle. Sorafenib alone is given in cycle 1, and HCQ is added in cycle 2. |
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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Toxicity evaluated according to the common toxicity criteria for adverse events (AEs) (CTCAEv4.0)
大体时间:2 years
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To assess the toxicities of combining sorafenib plus HCQ in this patient population
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2 years
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合作者和调查者
调查人员
- 首席研究员:Tyler Curiel, MD, MPH、University of Texas Health Science Center San Antonio
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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