A Phase 1b Study of Weekly Paclitaxel With Ramucirumab (IMC-1121B) Drug Product in Patients With Advanced Gastric Adenocarcinomas
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 With a Dose-Limiting Toxicity (DLT) During Cycle 1
研究概览
简要总结
Investigate the safety and tolerability of ramucirumab (IMC-1121B) drug product (DP) in combination with paclitaxel.
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
- •Has a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma
- •Has an advanced or metastatic solid gastric adenocarcinoma that has failed standard therapy
- •Has resolution of all clinically significant toxic effects of prior therapy, surgery, treatment with an investigational agent or device, treatment monoclonal antibody or small molecule, and radiotherapy or chemotherapy.
- •Has adequate organ function
- •Eligible participants of reproductive potential (both sexes) agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and for 12 weeks after the last dose of study medication
排除标准
- •Has undergone major surgery within 28 days prior to the study, or subcutaneous venous access device placement within 7 days prior to the study registration date
- •Has elective or planned surgery to be conducted during the trial
- •Has had treatment with an investigational agent or device, an antineoplastic small molecule, or antineoplastic radiotherapy or chemotherapy
- •Was previously treated with a chemotherapy regimen containing nitrosoureas or mitomycin C
- •Has had treatment with an antineoplastic monoclonal antibody within 8 weeks prior to the study registration date
- •Has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism prior to the study registration date
- •Has experienced any arterial thrombotic event, including myocardial infarction, cerebrovascular accident, or transient ischemic attack, within 6 months prior to the study date
- •Is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. (Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters International Normalized Ratio (INR) ≤ 1.5, prothrombin time (PT) and partial thromboplastin time (PTT) or - Is receiving chronic therapy with nonsteroidal anti-inflammatory agents [Aspirin use at doses up to 325 milligrams/day (mg/day) is permitted]
- •Has significant bleeding disorders, vasculitis, history of postoperative bleeding complications, hemoptysis or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to the study date
- •Has a history of GI perforation and/or fistulae within 6 months prior to the study 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 or peptic ulcer or bone fracture within 28 days prior to the study date
- •Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea
- •Has a serious illness or medical condition(s)
- •Is pregnant or lactating
- •Has received treatment with another investigational drug or participation in another interventional clinical trial within 28 days prior to the study date
研究组 & 干预措施
Ramucirumab (IMC-1121B ) and Pacitaxel
Each treatment cycle is 4 weeks (28 days)
干预措施: Ramucirumab (IMC-1121B ) (Biological)
Ramucirumab (IMC-1121B ) and Pacitaxel
Each treatment cycle is 4 weeks (28 days)
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Number of Participants With a Dose-Limiting Toxicity (DLT) During Cycle 1
时间窗: Cycle 1 of 28-day cycle
DLT based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE v4.02) in Cycle (Cy) 1 due to study drug (SD) with (w/): Grade (Gr) ≥3 neutropenia w/fever ≥38.5°C or w/bacteremia or sepsis, thrombocytopenia w/bleeding and platelet substitution, prothrombin and/or partial thromboplastin time w/no anticoagulation, hyperbilirubinemia; Gr 4: neutropenia \>5 days, thrombocytopenia, Gr 4 or uncontrollable hypertension QTc\>500 milliseconds (ms) or increase ≥100 ms increase in 24 hours after SD or significant arrhythmia in this period; Gr ≥3 nonhematologic toxicity (tox), excluding Gr 3 hypersensitivity, hypertension, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea w/out loperamide/nausea/vomiting w/out antiemetic and transient aminotransferase elevation. SD tox=delay \>1 week in ramucirumab (RAM) dose or omission of 1 dose of RAM or 2 paclitaxel doses due to tox in Cy 1 or delay \>2 weeks between Cy 1 and Cy 2 due to persistent tox.
Number of Participants With Adverse Events (AEs)
时间窗: Up to 47 weeks post baseline
The number of participants who experienced AEs of any grade, AEs of Grade ≥3 or AEs resulting in death that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of serious adverse events (SAEs) and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: Up to 47 weeks post baseline
The number of participants who experienced SAEs that were considered to be related to ramucirumab \[RAM (IMC-1121B)\] or paclitaxel (PAC). A summary of SAEs and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.
次要结局
- Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 1(Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 1(Cycle 1 Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Half-Life (t1/2) for Cycle 1(Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 3(Cycle 3: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Half-Life (t 1/2) for Cycle 3(Cycle 3: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Clearance (CL) for Cycle 3(Cycle 3: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 3(Cycle 3: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 4(Cycle 4: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 4(Cycle 4: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Half-Life (t 1/2) for Cycle 4(Cycle 4: Pre-infusion, Day 1 of 28-day cycle)
- Serum Anti-Ramucirumab Antibody Assessment (Immunogenicity)(Cycle 1 through Cycle 5 (28-day cycles))
- Ramucirumab Clearance (CL) or Cycle 1(Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 1(Cycle 1: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 2(Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Area Under the Concentration Time Curve (AUC) for Cycle 2(Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Half-Life (t1/2) for Cycle 2(Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Clearance (CL) for Cycle 2(Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 2(Cycle 2: Pre-infusion, Days 1, 2, 3, 5, 8, 12, and 15 of 28-day cycle)
- Ramucirumab Maximum Serum Concentration (Cmax) for Cycle 3(Cycle 3: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Clearance (CL) for Cycle 4(Cycle 4: Pre-infusion, Day 1 of 28-day cycle)
- Ramucirumab Steady State Volume of Distribution (Vss) for Cycle 4(Cycle 4: Pre-infusion, Day 1 of 28-day cycle)