Phase I Study of an Easy-to-Use Intravenous Formulation of Liposome Entrapped C-raf Antisense Oligonucleotide (LErafAON-ETU) Administered on a Weekly Schedule in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 4
- 主要终点
- To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of LErafAON-ETU.
研究概览
简要总结
The primary purpose of this study is to identify a dose of Liposome Entrapped c-raf Antisense Oligonucleotide Easy-to-Use (LErafAON-ETU) which maximizes potential benefits of the compound to patients with advanced cancer, without compromising their safety. This study will also assess the processing of LErafAON-ETU by the body over time. Patients will receive an intravenous infusion of LErafAON-ETU each week. Multiple blood samples will be taken for pharmacokinetic analysis during the first treatment; two samples will be taken during both the second and third treatments. Patients will be eligible to continue treatment until the occurrence of unacceptable toxicity or disease progression.
In LErafAON-ETU, antisense oligonucleotides specific to c-raf, are associated with liposomes, which are microscopic membrane-like structures created from lipids (fats). Raf-1 is a protein which plays a critical role in many aspects of cellular activation and growth. Therefore, it is thought to be an important factor that may support tumor development. LErafAON-ETU potentially limits the ability of a cell to produce the Raf-1 protein.
详细描述
This Phase I, open-label, dose-escalation study is designed to determine the maximum tolerated dose of LErafAON-ETU in patients who have advanced cancer considered unresponsive to available, conventional modalities or treatments. LErafAON-ETU will be administered as an IV infusion once weekly for 3 consecutive weeks (a Treatment Cycle). A complete pharmacokinetic profile of raf-1 antisense oligonucleotide will be assessed in week 1 only; limited pharmacokinetic sampling will be done prior to and at the end of infusion in weeks 2 and 3 only. Tumor/disease evaluation will be performed upon completion of 6 infusions (2 Cycles). Dose escalation will not occur until the safety and tolerability at a given dose level has been confirmed for 1 Cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •To be included in this study, patients must meet the following criteria:
- •Be ≥18 years of age.
- •Have advanced (local and/or metastatic) histologically documented cancer not considered responsive to available conventional modalities or treatment (i.e., no life prolonging therapy or therapy with a greater potential for patient benefit is available).
- •Have an ECOG Performance status of 0-
- •Have a life expectancy of >12 weeks.
- •Have recovered from acute toxicities of prior treatment: *No treatment with radiotherapy or with cytotoxic or biologic agents within 3 weeks prior to study entry. At least 2 weeks must have elapsed since any prior surgery or granulocyte-stimulating growth factor therapy. Chronic treatment with non-investigational gonadotropin-releasing hormone agonists or other hormonal or supportive care is permitted. Concurrent bisphosphonate treatment is permitted if initiated ≥90 days prior to study entry. *Chronic Grade 1 toxicities due to prior treatment or other causes are permitted.
- •Be in adequate condition as evidenced by the following clinical laboratory values:
- •Absolute neutrophil count (ANC) ≥1,500/mm³,
- •Hemoglobin ≥9.0 g/dL,
- •Platelets ≥125,000/mm³,
- •PT, aPTT, creatinine, calcium, and total bilirubin ≤the institutional upper limit of normal (ULN),
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN,
- •Alkaline phosphatase ≤2.5 x ULN
- •Patients (male and female) must be willing to practice an effective method of birth control during the study.
- •Patient must understand the investigational nature of this study and sign an Institutional Review Board (IRB) approved informed consent form prior to the performance of any study specific procedure.
排除标准
- •Patients are excluded from this study for the following:
- •Active uncontrolled bleeding or bleeding diathesis (e.g., active peptic ulcer disease).
- •Any active infection requiring parenteral or oral antibiotic treatment.
- •Known infection with human immunodeficiency virus or hepatitis virus.
- •Active heart disease including myocardial infarction within the previous 6 months, symptomatic coronary artery disease, arrhythmias currently requiring medication, or congestive heart failure.
- •Known or suspected active central nervous system metastasis (patients stable 8 weeks after completion of treatment for central nervous system metastasis are eligible).
- •Requiring immediate palliative treatment of any kind, including surgery and/or radiotherapy
- •Concurrent anti-tumor therapy (except for chronic hormonal anti-tumor therapy).
- •Treatment with any investigational drug within the 30-day period prior to enrollment in the study.
- •Known hypersensitivity to any of the components of LErafAON-ETU.
- •Prior treatment with LErafAON (previous sonicated formulation).
- •Female patients who are pregnant or breast-feeding.
- •Unwilling or unable to follow protocol requirements.
- •Any consideration which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug.
结局指标
主要结局
To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of LErafAON-ETU.
次要结局
- To determine the pharmacokinetics of raf antisense oligonucleotide after intravenous administration of LErafAON-ETU
- To determine any anti-tumor effects of LErafAON-ETU.