K-001 Treatment of Advanced Pancreatic Cancer: Phase I Clinical Trial of Monotherapy's Tolerability
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- The maximum-tolerated dose (MTD) of K-001
研究概览
简要总结
This study is an open and single-center Phase I clinical research on patients with advanced pancreatic cancer, for evaluating their adverse reactions or tolerance to K-001, so as to determine the safe and reasonable dosage and dosing regimen.
详细描述
According to past experience to toxicology studies and clinical test, K-001 at a dose of 2700mg/day has a good safety profile for human body. Upon observation, pancreatic cancer patients receiving a medication at 2160mg/day (1080mg BID) have had good therapeutic efficacy, no sign of significant toxicity.
Dosing regimen:
Phase I clinical test: maximum dose of monotherapy at 2700mg/day. Four groups of repeated administration of monotherapy, at least 3 patients for each group.
Group A: 2700mg/d (1350mg BID); Group B: 3240mg/d (1620mg BID); Group C: 3780mg/d (1890mg BID); Group D: 4320mg/d (2160mg BID). Twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.
In case of severe adverse reactions associated with the test drug, or if half of the participants show adverse reactions at Ⅲ level and above, the test should be terminated. The maximum dosage not causing the above-described situation shall be considered as the maximum tolerated dose or the biologically effective dose. After the test, continuous medication shall be given upon request from patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Disease-related criteria for inclusion:
- •Based on histodiagnosis or cytodiagnosis;
- •Locally advanced or metastatic pancreatic adenocarcinoma;
- •Failure of standard treatment, >28 days after the last chemotherapy;
- •Patients not suitable for or having given up standard treatment;
- •At least one lesion measurable according to RECIST V 1.0 criteria;
- •ECOG score: 0～1;
- •Expected survival: ≥3 months;
- •Haematological, biochemical and organ functions:
- •Hematological indices:
- •Absolute neutrophil count: ≥1.5×109/L;
- •Platelet count: ≥80×109/L;
- •Hemoglobin: ≥9.0 g/dL.
- •Total bilirubin: ≤1.5 x ULN, albumin: ≥3.0g/dL;
- •Patients without liver metastasis: ALT (SGPT) & AST (SGOT) ≤3.0 x ULN Patients with liver metastasis: ALT (SGPT) & AST (SGOT)≤5.0 x ULN;
- •Renal functions: serum creatinine ≤ 1.5xULN, Ccr ≥ 60ml/min (Cockcroft-Gault);
- •General criteria for inclusion:
- •Age: 18～70;
- •Letter of Consent signed by the patient or his/her legal representative:
- •Women of childbearing age must have a urine pregnancy test within 7 days before starting treatment, only negative results shall be included in the group. Male and female patients of childbearing age have agreed to use a reliable method of contraception before and during participating the study as well as 90 days (at least) after withdrawal.
排除标准
- •Disease-related criteria for exclusion:
- •Patients of pancreatic tumor but not adenocarcinoma;
- •Having received radiotherapy for his/her target lesions prior to this study, with no progress;
- •Known presence of brain metastases or leptomeningeal metastases;
- •With Vater's ampulla cancer or bile duct cancer;
- •Partial or complete intestinal obstruction;
- •History of other malignancies in past five years, except for:
- •A consecutive 5-year disease-free survival from single surgery of other malignancies;
- •Cured basal cell carcinoma and cured cervical carcinoma in situ.
- •General criteria for exclusion:
- •Pregnant or breast-feeding women;
- •Any unstable systemic disease, including: active infection; hypertension uncontrollable by medication (≥160/100mmHg); unstable angina, or angina with the onset from within the last three months; congestive heart failure (≥level II according to New York Heart Association [NYHA], see Annex 4); myocardial infarction occurred within 1 year before the enrollment; severe arrhythmias requiring medical treatment; and mental disorders, etc.;
- •Presence of active hepatitis B (history of hepatitis B infection, whether with or without medication, HBV DNA≥104 copy number or ≥2000u/ml) or HCV-Ab positive; known HIV-positive patients (no clinical signs or symptoms suggesting exemption of HIV test for HIV-infected individuals);
- •Having received any of the following treatment within specific time period before inclusion:
- •Having had a major surgery within 4 weeks before inclusion;
- •Having received expanded scope of radiotherapy within 4 weeks, or having received limited scope of radiotherapy within 2 weeks before inclusion;
- •Having participated in any other therapeutic/interventive clinical trials within 4 weeks before inclusion, or taking part in an ongoing trial.
- •With CTCAE toxicity at level II or above (excluding hair loss or skin pigmentation), uncured and caused by any previous treatment;
- •Not fitting in the study, as conceived by the researcher.
研究组 & 干预措施
Group A:K-001 2700mg/d (1350mg BID)
K-001 1350mg twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.
干预措施: K-001 (Drug)
Group B: K-001 3240mg/d (1620mg BID)
K-001 1620mg twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.
干预措施: K-001 (Drug)
Group C: K-001 3780mg/d (1890mg BID)
K-001 1890mg twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.
干预措施: K-001 (Drug)
Group D: K-001 4320mg/d (2160mg BID)
K-001 2160mg twice a day, to be taken with warm water on an empty stomach; 4 weeks' administration for each group.
干预措施: K-001 (Drug)
结局指标
主要结局
The maximum-tolerated dose (MTD) of K-001
时间窗: day 29
The maximum-tolerated dose (MTD) of K-001 will be defined as the maximum dose level at which no more than one patient out of three experiences a dose-limiting toxicity (DLT) using Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4.0. If none of the patient experiences DLT, the maximum dose in the trial (4320mg/d) will be defined as MTD and the biologically effective dose.
次要结局
- Change of life quality assessed using EORTC QLQ-C30 V 3.0(within 7 days before taking drugs and day 8, day 15, day 22 and day 29)
- Change from Baseline of the Treg cell count(within 14 days before taking drugs, day 15 and day 29)
- Evaluation of suffered pains assessed using Numerical Rating Scale (NRS)(within 7 days before taking drugs and day 8, day 15, day 22 and day 29)
- Change from Baseline of the C-reactive protein (CRP)(within 14 days before taking drugs, day 15 and day 29)
- Clinical efficacy of K-001 assessed by disease control rate (DCR) according to RECIST V 1.0 criteria(day 29)
研究者
Liwei Wang
Professor
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine