Phase II Trial of Cisplatin Combined With Oral TS-1 in Patients With Advanced Solid Tumors With Different Degrees of Liver Dysfunction
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Efficacy evaluations: Disease status
研究概览
简要总结
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
详细描述
Hepatic impairment is a common co-morbidity in cancer patients, particularly in those with extensive liver metastases. Decreased drug clearance as a result of impaired liver function may lead to increased systemic exposure and possibly greater toxicity. As many chemotherapeutic agents are metabolized by the liver, treatment options tend to be limited in patients with severe hepatic impairment, even in the presence of good performance status and adequate other organ function. Cisplatin is an active chemotherapeutic agent with broad spectrum activity that can safely be administered in severe hepatic impairment. Cisplatin has been combined safely with full dose oral TS-1 with good efficacy in a spectrum of solid tumors in patients with adequate renal and hepatic function.
The purpose of this study is to formally characterize the pharmacokinetics (PK), safety, and tolerability of TS-1 in combination with cisplatin in adult patients with advanced solid tumors who have mild, moderate or severe hepatic impairment relative to patients with normal hepatic function, as categorized by the United States National Cancer Institute organ dysfunction working group [NCI-ODWG] criteria for hepatic dysfunction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must fulfill ALL the following inclusion criteria
- •Age 18 years.
- •Histologic or cytologic diagnosis of carcinoma, that is either refractory to standard therapy or has no available therapies.
- •Measurable disease using the RECIST v1.1 criteria
- •ECOG performance 0 or
- •Estimated life expectancy of at least 12 weeks.
- •Adequate bone marrow and renal function as follows:
- •Bone marrow: Absolute neutrophil count (ANC) 1.5 x 109/L Platelets 100 x 109/L Renal: calculated creatinine clearance >60ml/minute Total bilirubin and AST/ALT as described in Table 1
- •Able to swallow pills
- •Signed informed consent from patient or legal representative
- •Patients with reproductive potential must use an approved contraceptive method if appropriate (e.g., intrauterine device, birth control pills, or barrier device) during and for three months after the study.
- •Females with childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
排除标准
- •Patients will be excluded from the study for any of the following reasons:
- •Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.
- •Treatment of a small molecule targeted agents ≤ 2 weeks prior to starting study treatment
- •Treatment within the last 30 days with any investigational drug.
- •Radiotherapy ≤4 weeks prior to starting study treatment or who have not recovered from radiotherapy-related toxicities. Limited field palliative radiotherapy ≤ 2 weeks prior to starting study treatment is allowed
- •Major surgery within 28 days of study drug administration.
- •History or presence of serious uncontrolled ventricular arrhythmias
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of TS-1 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
- •Known history of human immunodeficiency virus (HIV) seropositivity (HIV testing is not mandatory)
- •Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy.
- •Pregnancy.
- •Breast feeding.
- •Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator.
- •Poorly controlled diabetes mellitus.
- •Second primary malignancy that is clinically detectable at the time of consideration for study enrollment
- •Symptomatic brain metastasis.
- •History of significant neurological or mental disorder, including seizures or dementia.
研究组 & 干预措施
TS-1 combined with cisplatin
Eligible patients will be stratified by degree of liver dysfunction into 4 cohorts, in accordance to the National Cancer Institute Organ Dysfunction Working Group (NCI-ODWG) criteria
干预措施: TS-1 combined with cisplatin (Drug)
结局指标
主要结局
Efficacy evaluations: Disease status
时间窗: Radiological evaluation of tumor status every 2 cycles of cisplatin and oral TS-1 from baseline until documented disease progression; assessed up to 12 months
Efficacy evaluations will be performed using the RECIST v1.1 criteria Measurable disease: Tumor lesions: Must be accurately measured in at least one dimension (longest diameter in the plane of measurement is to be recorded) with a minimum size of 10mm on CT scan Malignant lymph node: ≥15mm in short axis on CT scan Non-measurable disease: All other lesions, including small lesions (longest diameter \<10mm or pathological lymph nodes with \>10 to \<15mm short axis) as well as truly non-measurable lesions
Efficacy Evaluation: Timing
时间窗: 5 years
The duration of tumor response is measured from the date of enrollment until the first date of documented disease progression or death due to any cause, whichever occurs first.
次要结局
未报告次要终点