Phase I Dose Finding and Pharmacokinetic Study of the Intravenous Camptothecin ST1968 in Patients With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 62
- 主要终点
- Maximum Tolerated Dose (MTD) of ST1968 given I.V. once every week for 2 consecutive weeks every 3 weeks and MTD of ST1968 given I.V. once every 3 weeks
研究概览
简要总结
ST1968 is a novel camptothecin derivative which interacts with topoisomerase I-DNA complex, inducing S-Phase specific cytotoxicity. It is endowed with a potent antitumor activity and an increased Therapeutic Index with respect to the clinically used analogues (i.e.irinotecan and topotecan) in some xenograft models (ovary, colon, head & neck, cervix). Anti-tumor activity has been also noted in platinum resistant ovarian cell xenografts and in topoisomerase I mutant prostate cell lines. The acceptable toxicity profile in animals and the activity in camptothecin-resistant cell lines make ST1968 a good candidate for clinical trials.
详细描述
Multicenter, open label, uncontrolled Phase I pharmacokinetic trial to determine the Maximum Tolerated Dose (MTD) of ST1968 given intravenously (I.V.) once every week for 2 consecutive weeks every 3 weeks and the MTD of ST1968 given I.V. once every 3 weeks. A starting dose of 1.5mg/m2 given as a flat dose of 2.5mg is defined, given once on Day 1, Day 8 every 21 Days (D1, D8 Q21D schedule), over 2 h. Starting dose for the Day 1 every 21 Days (D1 Q21D schedule) has to be determined from the MTD of D1, D8 Q21D schedule.
Plasma, urine pharmacokinetics in all patients (minimum of 3 pts for each cohort) during the first cycle of treatment and in at least 6 patients at the Recommended Dose (RD).
During the study any hints of anti-tumor activity will also be evaluated by RECIST criteria.
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
- •Histological/cytological diagnosis of solid tumors for which therapy of proven efficacy does not exist.
- •Preferably measurable disease
- •ECOG performance status ≤
- •Age ≥ 18 years.
- •Ongoing toxicity associated with prior anticancer therapy ≤ grade 1 (NCI-CTCAE V3.0).
- •Maximum of 2 prior chemotherapy lines for advanced disease (not including neoadjuvant or adjuvant chemotherapy)
- •Adequate hematological, liver and renal function
- •Hemoglobin ≥ 9 g/dl; ANC ≥ 1.5 x 109/L; platelets ≥ 100 x 109/L;
- •Serum bilirubin ≤ upper normal limit (UNL). ALT, AST ≤ UNL but ≤ 2.5 x UNL in case of liver metastases; alkaline phosphatase (liver isoenzyme fraction) ≤ UNL or ≤ 1.5xULN in case of liver metastases; albumin within normal limits;
- •Creatinine ≤1.5 mg/dl or calculated creatinine clearance ≥ 60 ml/min.
- •Life expectancy of at least 3 months
- •Capacity of understanding the nature of the trial and giving written informed consent.
排除标准
- •Less than 4 weeks since last chemotherapy, radiotherapy or prior investigational therapy. Less than 2 weeks since last hormone or immunotherapy or signal transduction therapy.
- •Active infection.
- •Presence of cirrhosis or chronic hepatitis
- •Presence of serious cardiac (congestive heart failure, angina pectoris, myocardial infarction within one year prior to study entry, uncontrolled hypertension or arrhythmia), neurological or psychiatric disorder.
- •Presence of uncontrolled intercurrent illness or any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study.
- •Symptomatic brain metastases (this does not include primary brain tumors) or leptomeningeal disease.
- •Pregnancy or lactation or unwillingness to use adequate method of birth control
研究组 & 干预措施
ST1968
ST1968 once a week for 2 weeks every 3 weeks (protocol amendment: once every 3 weeks
干预措施: ST1968 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of ST1968 given I.V. once every week for 2 consecutive weeks every 3 weeks and MTD of ST1968 given I.V. once every 3 weeks
时间窗: 21 days
2/6 patients with a Dose Limiting Toxicity (DLT) at the first cycle (21 days)
次要结局
- Adverse events, physical examination and laboratory tests (hematology and biochemistry) as a measure of safety and tolerability(21 days of each cycle of therapy)
- Tumor response(4 weeks)
- Tmax, Cmax, AUC0-24, AUC-last, T1/2,CL(21 days)