A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Docetaxel Lipid Microsphere for Injection in Cancer Patients Receiving Chemotherapy
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- The safety and tolerability
研究概览
简要总结
Docetaxel Lipid Microsphere (DT-LM) is a novel proprietary delivery system of docetaxel developed by Shenyang Pharmaceutical University. In this Phase I study, the DT-LM was evaluated for the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) in patients with advance solid tumors. It was also evaluated for pharmacokinetic and anti-tumor effects of DT-LM compared to commerical docetaxel.
详细描述
Docetaxel (currently marketed as Taxotere®), given by intravenous or intraperitoneal injection, has contributed significantly to the treatment of a variety of malignancies, such as ovarian, breast, gastric, and non-small-cell lung cancer (NSCLC), as well as head and neck cancer and some other cancers. In the preclinical, DT-LM showed reduced toxicity (especially myelosuppression）and comparable therapeutic efficacy. In clinic, it is believed that DT-LM will offer fewer side effects to the patient at similar doses, and possibly greater effectiveness when used at higher doses. DT-LM could not only avoid the serious hypersensitivity reactions caused by Tween 80, but also be stable, safe and convenient for clinical administration.
This study is designed to determine the following:
- The maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of DT-LM.
- The pharmacokinetics of docetaxel following intravenous administration of DT-LM.
- Any anti-tumor effects of DT-LM.
Controlled trial is also carrying out to reveal the differences in safety, pharmacokinetics and pharmacodynamics between DT-LM and Taxotere.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 and < 65, with ECOG performance status 0-1,and Life expectancy of more than 3 months.
- •Have advanced (local and/or metastatic) histologically documented cancer considered unresponsive to available conventional modalities or treatments.
- •Have recovered from acute toxicities of prior treatment:
- •4 weeks must have elapsed since receiving any investigational agent.
- •4 weeks must have elapsed since receiving any radiotherapy, or treatment with cytotoxic or biologic agents (≥6 weeks for mitomycin or nitrosoureas).
- •4 weeks must have elapsed since any prior surgery.
- •Be in adequate condition as evidenced by the following clinical laboratory values:
- •Absolute neutrophil count (ANC) ≥1,500/mm
- •Platelets ≥ 80,000/mm
- •Hemoglobin ≥ 9.0 g/dL.
- •WBC ≥ 4,000/mm
- •Total bilirubin ≤ 2.5 x institutional upper limit normal (ULN).
- •Transaminases AST (SGOT) and ALT (SGPT) ≤ 1.5 times ULN or ≤ 5 times ULN (liver metastasis).
- •Serum creatinine ≤ 1.2 times ULN, blood urea nitrogen≤ 1.2 times ULN.
- •both female and male patients must use adequate methods of contraception.
- •Patient or legal representative must understand the investigational nature of this study and sign an Institutional Review Board (IRB)/Independent Ethics Committee approved written informed consent form prior to treatment.
排除标准
- •Intolerance to any antineoplastic agents belonging to the taxoid family.
- •having failed a docetaxel-containing regimen or Having known non-controllable hypersensitivity to docetaxel or lipid microsphere.
- •Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
- •Unstable or uncontrolled cardiac disease or hypertension.
- •With other serious internal diseases, uncontrolled infection or uncontrolled diabetes.
- •With Symptomatic brain metastasis not controlled.
- •Having pre-existing clinically significant neuropathy (NCI CTCAE Grade ≥ 2 neuromotor or Grade ≥ 2 neurosensory) except for abnormalities due to cancer.
- •Currently receiving any other standard or investigational treatment for cancer or any other investigational agent for any indication.
- •Requiring immediate palliative treatment of any kind including surgery and/or radiotherapy.
- •Female patients who are pregnant or breast-feeding.
- •Unwilling or unable to follow protocol requirements.
- •With history of serious allergic or allergy.
- •Not fit for the clinical trial judged by the investigator.
研究组 & 干预措施
DT-LM
Docetaxel Lipid Microsphere (DT-LM)
干预措施: DT-LM (Drug)
Taxotere
Commerical Product
干预措施: docetaxel (Drug)
结局指标
主要结局
The safety and tolerability
时间窗: one year
This Phase I, open-label, control,dose-escalation study was designed to determine the maximum tolerated dose (MTD) of DT-LM in patients with advanced cancer. DT-LM was administered by intravenous infusion, over 1 hour, once every 21 days until occurrence of disease progression or toxicity requiring early treatment discontinuation. Dose escalation was not done until the safety and tolerability at a given dose level has been confirmed.
次要结局
- Assessment of pharmacokinetics of DT-LM and Taxotere: AUC and Cmax(one year)
- Objective tumour response according to RECIST(one year)
研究者
Shi Yuankai, Ph.D
the Director of Oncology Department
Chinese Academy of Medical Sciences