NCT01238939已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose
研究概览
简要总结
The primary objective is to determine the maximum tolerated dose/recommended phase II dose of the combination regimen of NK012 and 5-fluorouracil in patients with advanced solid tumors.
详细描述
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 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-
- •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^
- •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.
排除标准
- •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.
研究组 & 干预措施
Treatment
Experimental
干预措施: NK012 and 5-FU (Drug)
结局指标
主要结局
Number of patients with dose-limiting toxicity as determinant of the maximum tolerated dose/recommended dose
时间窗: From date of first dose to off-study (or 30 days since last dose)
次要结局
- Number of patients with adverse events as a measure of safety and tolerability(From date of first dose to off-study (or 30 days since last dose))
- Tumor measurements, as a measure of efficacy(Baseline, then every on average every 2 months until off-study)
- Area under the plasma concentration versus time curve (AUC) of NK012 and fluorouracil(15,30min, 1,6,24,46.5,48,72hrs, Wk1,2,3,4 of cycle 1)
- Peak Plasma Concentration (Cmax) of NK012 and fluorouracil(15,30min, 1,6,24,46.5,72hrs, week 1,2,3,4 of cycle 1)
研究者
研究点 (1)
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