Study of NK012 and 5-FU/LV in Solid Tumors Followed by Dose Expansion in Colorectal Cancer
A Phase I Study of NK012 in Combination With Infusional 5-fluorouracil and Leucovorin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Metastatic Colorectal Cancer
研究概览
详细说明
On Day 1 of each 28 day cycle, NK012 will be administered as a 30 minute IV infusion, followed by continuous infusion of 5-FU over 46 hours. On Day 15 of each cycle, patients again receive 5-FU continuous infusion. Treatment is expected to continue for 6 cycles, unless disease progression or the development of unacceptable toxicity requires discontinuation of the drug. At the discretion of the investigator, patients who show signs of benefit may continue beyond 6 cycles.
Once a MTD/RD has been determined for the combination regimen, a dose expansion cohort of patients with metastatic colorectal cancer will be treated at the determined MTD.
(Prior to Amendment 2, patients were receiving NK012 and 5-FU and leucovorin (LV). The dosing regimen was changed as of Amendment 2 to NK012 and 5-FU.)
研究类型
注册 (预期的)
阶段
- 阶段1
联系人和位置
学习地点
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Tennessee
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Nashville、Tennessee、美国
- Sarah Cannon Research Institute
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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:
- Histologically or cytologically confirmed diagnosis of advanced solid tumor for which no efficacious therapy exists, or for which a camptothecin-based regimen would be appropriate.
For the dose expansion at MTD/RD only:
- The patient must have failed oxaliplatin-based first line therapy for metastatic colorectal cancer. This includes patients who failed oxaliplatin-based therapy with progressive disease, as well as patients who, based on toxicity or MD/patient discretion, are no longer candidates for oxaliplatin. Patients who failed adjuvant therapy with oxaliplatin-based chemotherapy regimens within one year of last dose of oxaliplatin-based chemotherapy will also be considered eligible for this study.
- Patients must have had no more than one prior chemotherapy regimen in the metastatic setting. Patients who had radiosensitizing chemotherapy during radiation treatment will not have this treatment count as a prior chemotherapy regimen.
- Patients must have measurable disease by RECIST (version 1.1).
- Patient must have recovered from all acute adverse effects of prior therapies, excluding alopecia.
- For patients enrolled in the dose escalation phase, no more than 4 prior cytotoxic regimens in the metastatic setting.
- Prior irradiation to no more than 25% of the bone marrow.
- ECOG performance status of 0-1.
- Life expectancy of at least 12 weeks.
- Patients are at least 18 years of age.
- Adequate bone marrow function as defined by ANC ≥ 1500/mm^3 and platelet count ≥ 100,000/mm^3.
- AST and ALT ≤ 3.0 x ULN (5 x ULN if documented liver metastases) and total bilirubin ≤ 1.5 x ULN.
Serum creatinine ≤ 1.5 x ULN, or creatinine clearance ≥ 60 mL/min by Cockcroft-Gault formula* for patients with serum creatinine > 1.5 x ULN.
*Cockcroft-Gault formula for creatinine clearance (CrCl): Males: CrCl (ml/min) = (140 - age) x wt (kg) / (serum creatinine x 72) Females: Multiply the above result by 0.85
- Able to understand and show willingness to sign a written informed consent document.
Exclusion Criteria:
- Prior chemotherapy, radiation therapy, or investigational therapy within 4 weeks (exception: 6 weeks for nitrosoureas or mitomycin C); or prior non-cytotoxic therapy within 5 drug half-lives (or 4 weeks, which ever is shorter); or monoclonal antibodies within 4 weeks prior to the first dose of study treatment.
- Concurrent use of other investigational agent.
- History of brain metastases or spinal cord compression, unless irradiated or treated a minimum of 4 weeks prior to first study treatment and stable without requirement of corticosteroids for > 1 week.
- Concurrent serious infections requiring parenteral antibiotic therapy.
- Pregnant or of childbearing potential and not using methods to avoid pregnancy. A negative pregnancy test must be documented at baseline for women of childbearing potential. Patients may not breast-feed infants while on this study.
- Significant cardiac disease including heart failure that meets NYHA class III and IV definitions, history of myocardial infarction within 6 months of study entry, uncontrolled dysrhythmias or poorly controlled angina.
- History of serious ventricular arrhythmia (VT or VF, ≥ 3 beats in a row), QTc ≥ 450 msec for men and 470 msec for women, or LVEF ≤ 40% by MUGA or ECHO.
- History of allergic reactions attributed to compounds of topoisomerase I inhibitors.
- Prior treatment with irinotecan.
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:治疗
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NK012 infusion on Day 1 of each 28 day cycle 5-FU continuous infusion on Days 1 and 15 of each 28 day cycle
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研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
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具有剂量限制性毒性作为最大耐受剂量/推荐剂量决定因素的患者人数
大体时间:从第一次给药之日到研究结束(或自最后一次给药后 30 天)
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从第一次给药之日到研究结束(或自最后一次给药后 30 天)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
发生不良事件的患者人数作为安全性和耐受性的衡量标准
大体时间:从第一次给药之日到研究结束(或自最后一次给药后 30 天)
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从第一次给药之日到研究结束(或自最后一次给药后 30 天)
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Tumor measurements, as a measure of efficacy
大体时间:Baseline, then every on average every 2 months until off-study
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Efficacy, based on RECIST 1.1, will be assessed in all solid tumors, and in a specific subset of patients with colorectal cancer
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Baseline, then every on average every 2 months until off-study
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Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil
大体时间:15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1
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15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1
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Peak Plasma Concentration (Cmax) of NK012 and fluorouracil
大体时间:15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1
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15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1
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合作者和调查者
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
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.
NK012 and 5-FU的临床试验
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Sol-Gel Technologies, Ltd.完全的
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Catharina Ziekenhuis Eindhoven招聘中5-FU的TDM | 药代动力学观察研究荷兰
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Chia Tai Tianqing Pharmaceutical Group Co., Ltd.未知