A Phase I Dose-Escalation, Pharmacokinetic and Pharmacodynamic Evaluation of Intravenous LY2275796 in Patients With Advanced Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of LY2275796
研究概览
简要总结
Primary Objective:
- To determine a recommended Phase 2 dose of LY2275796 that may be safely administered to patients with advanced cancer, with prospects for therapeutic biologic effects. This will require simultaneous:
- monitoring of toxicities & determination of maximal tolerated dose (MTD)
- detecting eIF-4E target inhibition in tumor
- pharmacokinetic measurements
Secondary Objectives:
- To estimate pharmacokinetic parameters of LY2275796 and explore pharmacokinetic/pharmacodynamic relationships
- To document any antitumor activity observed with LY2275796
详细描述
LY2275796 is designed to block the effect of a cancer-promoting gene called eIF-4E (eukaryotic initiation factor 4E).
Before you can receive the drug on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. Your complete medical history will be recorded and you will have a physical exam. You will have an electrocardiogram (ECG -- a test that measures the electrical activity of the heart). You may also have x-rays, computed tomography (CT) scans, or magnetic resonance imaging, whichever imagining your doctor thinks is best to monitor the status of the disease.
Blood (about 3 tablespoons) will be drawn for routine tests and to measure how the drug moves around inside your body and effects your body. Your blood sample will also be tested for human immunodeficiency virus (HIV, the virus that causes AIDS), Hepatitis B, and Hepatitis C. If your test results show that you have HIV, Hepatitis B, or Hepatitis C, you will be notified and given information about counseling services. The results of your HIV, Hepatitis B, and Hepatitis C tests will be kept confidential and disclosed only as required by law. If you do not take these tests for Hepatitis B, Hepatitis C, or HIV, or if you test positive for any of these, you will not be eligible for this study. If there is more than a 2-week delay before beginning the study, these tests may need to be repeated. Within 3 days of receiving the study drug, women who are able to have children must have a negative blood pregnancy test.
If you are found eligible to take part in this study, LY2275796 will be given by an infusion into your vein over 3 days. This is called a loading dose of the study drug and the purpose is to make sure the tumor tissue gets enough of the study drug for it to target the disease. This dose will be given either as 3 separate 3-hour infusions by vein for 3 days in a row or as a nonstop infusion for 3 days (72 hours).
The way you receive the drug will be decided by your study doctor and the study sponsor. This decision will be based upon the dose of the study drug that you are to receive and on the information gathered from other participants who have already received the study drug. Whichever way you are to receive the study drug, you may have to stay in the hospital for the first 3 days. Days 1-7 will be considered Cycle 1 of this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Evidence of histologically or cytologically documented malignancy, including patients with treated, stable brain metastases. For Part A: Malignancy that is advanced and/or metastatic for which no proven therapy exists (for example, there is no comparable or satisfactory alternative drug or other therapy available to treat that stage of the disease). For Part B and C: Malignancy that is advanced and/or metastatic for which no proven therapy exists, and presents with disease that is amenable to serial measurement of pharmacodynamics by biopsy.
- •Male or female >/= 18 years of age
- •Written informed consent from the patient
- •Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- •Patients must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or other investigational therapy for at least 4 weeks (2 weeks for palliative radiotherapy, 6 weeks for mitomycin C or nitrosoureas), prior to study enrollment and have recovered from the acute effects of therapy.
- •Patients are able to comply with the protocol requirements and are reliable and willing to make themselves available for the duration of the study and will abide by the research units policies and procedures.
- •Have adequate organ function including: Bone Marrow Reserve: Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L prior to treatment, platelets >/= 100 x 10^9/L, hemoglobin >/= 9 g/dL; Hepatic: Bilirubin </= upper limits or normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) </= 2.5 x ULN; Renal: Calculated creatinine clearance by Cockcroft-Gault formula >/= 50 ml/min; Coagulation: Activated prothrombin time (APTT) and prothrombin time (PT) less than or equal to the ULN.
- •Males and females with reproductive potential should use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug.
排除标准
- •Patient with current hematological malignancies or bleeding diathesis
- •Serious pre-existing medical conditions at the discretion of the investigator
- •Major surgery within 4 weeks of study enrollment
- •Women who are pregnant or lactating
- •Symptomatic central nervous system (CNS) neoplasm. (Patients who have CNS neoplasms stable on steroid medication may be included.)
- •Concomitant anticancer therapy or anticoagulant therapy (with the exception of the use of heparinized saline to maintain the patency of central venous catheters).
- •Patients who require palliative radiotherapy at the time of study entry
- •Previous treatment with antisense therapies
- •Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication
- •Presence of positive test results in HIV antibodies, Hepatitis B surface antigen, or Hepatitis C antibodies (Rationale: Correlative biologic studies entail aerosolization of biologic fluids. Researchers use Universal precautions and should be protected from HIV or Hepatitis viruses. However, robotic equipment handling specimens with high viral load would require purging and sterilization procedures that could damage the equipment or alter results for subsequent specimens. Patients lacking symptoms or signs of HIV or hepatitis have low viral loads so that screening for them is not necessary).
研究组 & 干预措施
LY2275796
干预措施: LY2275796 (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of LY2275796
时间窗: Dose toxicity with each loading dose (daily for 3 days) then weekly
Maximum tolerated dose (MTD) defined as highest dose at which 0-1/6 patients experience Grade III toxicity with LY2275796 administered IV as a loading dose daily over 3 days, then as maintenance dose weekly.
次要结局
未报告次要终点