A Phase 1b Study of Irinotecan, Levofolinate, and 5-Fluorouracil (FOLFIRI) Plus Ramucirumab (IMC-1121B) Drug Product in Japanese Subjects With Metastatic Colorectal Carcinoma Progressive During or Following First-Line Combination Therapy With Bevacizumab, Oxaliplatin, and a Fluoropyrimidine
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
研究概览
简要总结
The primary objective of this study is to investigate the safety and tolerability of the anti-vascular endothelial growth factor receptor-2 (anti-VEGFR-2) monoclonal antibody Ramucirumab (IMC-1121B) in combination with irinotecan, levofolinate, and 5-fluorouracil (FOLFIRI) in Japanese participants with advanced colorectal carcinoma (CRC).
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant is Japanese
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has histologically or cytologically confirmed CRC
- •Has metastatic disease that is not amenable to potentially curative resection
- •Has received no more than 2 prior systemic chemotherapy regimens in any setting (only 1 prior regimen for metastatic disease is permitted)
- •Has received first-line combination therapy of bevacizumab, oxaliplatin, and a fluoropyrimidine for metastatic disease and has experienced disease progression during first-line therapy, or disease progression within 6 months after the last dose of first-line therapy, or discontinued part or all of first-line therapy due to toxicity and experienced disease progression within 6 months after the last dose of first-line therapy. Participants must have received a minimum of 2 doses of bevacizumab as part of a first-line regimen containing chemotherapy in order to enroll.
- •Has adequate hepatic, renal, hematologic, and coagulation function
- •The participant's urinary protein is ≤1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria ≥2+, then a 24-hour urine must be collected and must demonstrate <1000 milligrams (mg) of protein in 24 hours to allow participation in the study
排除标准
- •Has received bevacizumab within 28 days prior to study registration
- •Has received chemotherapy within 21 days prior to study registration
- •Has received any previous systemic therapy (other than a combination of bevacizumab, oxaliplatin, and a fluoropyrimidine) for first-line treatment of metastatic CRC
- •The participant experienced any of the following during first-line therapy with a bevacizumab-containing regimen: an arterial thrombotic/thromboembolic event; Grade 4 hypertension; Grade 4 proteinuria; a Grade 3-4 bleeding event; or bowel perforation
- •Has received wide-field (full-dose pelvic) radiotherapy within 28 days prior to study registration
- •Has undergone major surgery within 28 days or subcutaneous venous access device placement within 7 days prior to study registration
- •Has elective or planned surgery to be conducted during the trial
- •Has a history of deep vein thrombosis or pulmonary embolism within the past 12 months
- •Has experienced any arterial thrombotic event within the past 12 months
- •Participant is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents
- •Participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents [Aspirin up to 325 milligrams per day (mg/day) permitted]
- •Has a significant bleeding disorder or has had a significant (Grade 3 or higher) bleeding event within 3 months prior to registration date
- •Has a history of gastrointestinal perforation and/or fistulae within 6 months prior to registration date
- •Has symptomatic congestive heart failure, unstable angina pectoris, or symptomatic or poorly controlled cardiac arrhythmia
- •Has uncontrolled arterial hypertension despite standard medical management
- •Has a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to study registration
- •Has an acute/subacute bowel obstruction or history of clinically significant chronic diarrhea
- •Has a history of inflammatory bowel disease or Crohn's disease requiring medical intervention within 12 months prior to registration date
- •The participant has either peptic ulcer disease associated with a bleeding event or known active diverticulitis
- •Has an active infection requiring antibiotic, antifungal, or antiviral therapy
- •Has known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)-related illness
- •Has known leptomeningeal or brain metastases or uncontrolled spinal cord compression
- •Has a known history of Gilbert's Syndrome, or is known to have any of the following genotypes: uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*6/*6; UGT1A1*28/*28 or UGT1A1*6/*28
- •Has previous or concurrent malignancy, except for basal or squamous cell skin cancer and/or in situ carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years
研究组 & 干预措施
FOLFIRI plus Ramucirumab (IMC-1121B)
干预措施: Ramucirumab (IMC-1121B) (Biological)
FOLFIRI plus Ramucirumab (IMC-1121B)
干预措施: Irinotecan (Drug)
FOLFIRI plus Ramucirumab (IMC-1121B)
干预措施: levofolinate (Drug)
FOLFIRI plus Ramucirumab (IMC-1121B)
干预措施: 5-Fluorouracil (5-FU) (Drug)
结局指标
主要结局
Number of Participants That Experienced Any Dose-Limiting Toxicities (DLT) During the DLT Assessment Period
时间窗: Day 1, Cycle 1 through Day 1, Cycle 3 (1 cycle=14 days)
DLTs were adverse events (AEs) possibly related to study drug that met the National Cancer Institute's Common Terminology Criteria for AEs (NCI CTCAE, version 4.03): Grade 4 neutropenia ≥7 days or ≥Grade 3 with bacteremia or sepsis; Absolute neutrophil count \<1.0x10\^9/Liters with fever ≥38.3°Celsius requiring intravenous antibiotic therapy; Grade 4 thrombocytopenia or ≥Grade 3 with bleeding requiring platelet transfusion; ≥Grade 3 altered coagulation tests and no anticoagulation; ≥Grade 4 or uncontrolled hypertension; ≥Grade 3 non-hematologic toxicity (except non-clinically significant Grade 3 events like electrolyte abnormality, hypersensitivity, and arthralgia/myalgia); urine protein \>3 grams/24 hours; study drug-related toxicity causing Cycle 3, Day 1 treatment delay until Day 44 or later. Grade 3 or Grade 4 infusion-related reaction (hypersensitivity) due to ramucirumab or FOLFIRI, not a DLT.
Number of Participants With Ramucirumab Drug-Related Adverse Events or Serious Adverse Events
时间窗: Baseline to end of study (up to 49.3 weeks) plus 37 day follow-up
Data are presented for the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade ≥3 TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. Events related to Irinotecan, Levofolinate, and 5-fluorouracil (5-FU) were reported separately. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.
次要结局
- Number of Participants With Serum Anti-IMC-1121B Antibodies (Immunogenicity)(Day 1 of Cycle 5 (Week 9), Cycle 6 (Week 11), Cycle 7 (Week 13), and Cycle 9 (Week 17) [(1 cycle=14 days)])
- Maximum Concentration (Cmax) of Ramucirumab(Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days))
- Steady State Volume of Distribution (Vss) of Ramucirumab(Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days))
- Half Life (t1/2) of Ramucirumab(Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days))
- Clearance (CL) of Ramucirumab(Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days))
- Area Under the Curve (AUC) of Ramucirumab(Day 1, Cycle 1 and Day 1, Cycle 5 (1 cycle=14 days))
- Best Overall Response [Anti-Tumor Activity of FOLFIRI Plus Ramucirumab (IMC-1121B)](Every 8 weeks until PD (up to 49 weeks))