A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Irinotecan and Its Metabolite SN-38 When Coadministered With Folinic Acid and 5 Fluorouracil in Patients With Advanced Malignant Solid Tumors
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Irinotecan and Its Metabolite SN-38 From Time Zero to Infinity [AUC(0-∞)] in Cycle 1
研究概览
简要总结
The purpose of this study is to assess the effect of concomitant ramucirumab (IMC-1121B) on the pharmacokinetics of irinotecan and its metabolite SN-38 when coadministered with folinic acid and 5-fluorouracil, in participants with advanced malignant solid tumors resistant to standard therapy or for which no standard therapy is available.
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
- •Has histologic or cytologic documentation of a malignant solid tumor
- •Has an advanced solid tumor that is resistant to standard therapy or for which no standard therapy is available
- •Has resolution to Grade ≤1, per the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v. 4.0), of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Has adequate hematologic, coagulation, and hepatic function
- •Has serum creatinine ≤ 1.5 x upper limit of normal (ULN)
- •Urinary protein is <2+ on dipstick or routine urinalysis (UA) at study entry
- •Women with childbearing potential must have a negative serum or urine pregnancy test
- •Eligible participants of reproductive potential (both sexes) agree to use adequate method of contraception during the study period and for 12 weeks after the last dose of study medication
排除标准
- •Has received a therapeutic monoclonal antibody within the last 42 days
- •Has received cytotoxic chemotherapy within the last 21 days
- •Has received radiotherapy within the last 14 days
- •Are currently enrolled in, or discontinued within the last 14 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the last 3 months
- •Has an uncontrolled illness, including, but not limited to uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders
- •Has experienced any arterial thromboembolic event within the last 6 months
- •Has known leptomeningeal disease or brain metastases or uncontrolled spinal cord compression
- •Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
- •Has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness
- •Has received a prior organ or transplantation
- •Has undergone major surgery within the last 28 days
- •Has had a serious nonhealing wound, ulcer, or bone fracture within the last 28 days
- •Has an elective or planned major surgery to be performed during the course of the trial
- •Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
- •Has experienced a Grade 3 or higher bleeding event within the last 3 months
- •Has a known history or clinical evidence of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase isoform 1A1 (UGT1A1)*6/*6, UGT1A1*28/*28, or UGT1A1*6/*28
- •Has received clinically relevant inhibitors or inducers of cytochrome P (CYP) 450 CYP3A4/5 or CYP2C9 and/or isoenzymes within the last 3 weeks
- •Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis and a history of hepatic encephalopathy, or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
研究组 & 干预措施
ramucirumab (IMC-1121B) and FOLFIRI
Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle).
干预措施: Ramucirumab (IMC-1121B) (Biological)
ramucirumab (IMC-1121B) and FOLFIRI
Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle).
干预措施: Irinotecan (Drug)
ramucirumab (IMC-1121B) and FOLFIRI
Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle).
干预措施: Folinic acid (Drug)
ramucirumab (IMC-1121B) and FOLFIRI
Treatment is sequential, Ramucirumab (IMC-1121B) will be administered before FOLFIRI ((Irinotecan + Folinic acid + 5-Fluorouracil). FOLFIRI will be administered each cycle and Ramucirumab (IMC-1121B) will be administered beginning from Cycle 2 (2-week cycle).
干预措施: 5-Fluorouracil (Drug)
结局指标
主要结局
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Irinotecan and Its Metabolite SN-38 From Time Zero to Infinity [AUC(0-∞)] in Cycle 1
时间窗: Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geometric Least Squares (Geo LS) means. Geo LS means were adjusted for cycle, participant and random error.
Pharmacokinetics: Dose-Normalized AUC(0-∞) of Irinotecan and Its Metabolite SN-38 in Cycle 2
时间窗: Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
Dose-normalized AUC(0-∞) was calculated from AUC(0-∞) divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error.
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Irinotecan and Its Metabolite SN-38 in Cycle 1
时间窗: Cycle 1: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error.
Pharmacokinetics: Dose-Normalized Cmax of Irinotecan and Its Metabolite SN-38 in Cycle 2
时间窗: Cycle 2: 0, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 22, 25, 28, 31, 34, 48, 72, 96 and 168 hours post-irinotecan infusion
Dose-normalized Cmax was calculated from Cmax divided by the dose. Data presented are Geo LS means. Geo LS means were adjusted for cycle, participant and random error.
次要结局
- Pharmacokinetics: Cmax of Ramucirumab (IMC-1121B)(Cycle 2: -2, -1, -0.5, 0, 2, 3, 4, 5, 8, 10, 25, 48, 72, 96, 168, 264, 336 hours post-ramucirumab (IMC-1121B) infusion)
- Number of Participants With Treatment Emergent Anti-Drug Antibodies (TE-ADA)(Up To 2 Years)