Phase I Study of Ramucirumab in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
研究概览
简要总结
This trial is testing ramucirumab (LY3009806) administered to Chinese participants with advanced solid tumors that are resistant to standard therapy or for whom no standard therapy is available. The purpose of this study is to evaluate how safe ramucirumab is and whether it causes any side effects. The study will also measure how much ramucirumab gets into the blood stream and how long it takes the body to get rid of it.
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
- •Chinese participants with histopathologically or cytologically diagnosed advanced solid tumor
- •Did not respond to standard therapy or no standard therapy is available
- •Measurable or nonmeasurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST)
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 at study entry
- •Able to provide written informed consent
- •A life expectancy of >3 months
- •Adequate hematologic function, as defined by: Absolute neutrophil count (ANC) ≥1500 per cubic millimeter (mm^3); hemoglobin concentration ≥9 grams per deciliter (g/dL); and platelet count ≥100,000/mm^3
- •Adequate hepatic function, as defined by: Total bilirubin level ≤1.5 x the upper limit of normal (ULN) (in participants with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN with direct bilirubin ≤ 1.5 x ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (or ≤5 x ULN if the participant has liver metastases
- •Adequate renal function, as defined by: Serum creatinine level ≤1.5 x ULN; or calculated serum creatinine clearance (Cockcroft-Gault) ≥50 milliliters per minute (mL/min)
- •Urinary protein is 0 or 1+ on dipstick but no edema nor serum albumin < lower level of normal
- •Adequate coagulation function, as defined by: International normalized ratio (INR) ≤1.5, or prothrombin time (PT) ≤1.5 x ULN and activated partial thromboplastin time (aPTT) ≤1.5 x ULN (unless receiving anticoagulation therapy)
- •Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study treatment
排除标准
- •Had chemotherapy or therapeutic radiotherapy within 14 days (6 weeks for nitrosoureas or mitomycin C) before entering the study or the participant has ongoing side effects (≥ Grade 2) due to previously administered agents
- •Has obvious evidence of intratumor cavitation
- •Has undergone major surgery within 28 days before study entry or has had a central venous access device inserted within 7 days before study entry
- •Has a history of gastrointestinal perforation, postoperative bleeding complications, or wound complications from a surgical procedure
- •Has elective or planned surgery to be conducted during the trial
- •Has documented and/or symptomatic brain or leptomeningeal metastases
- •Has uncontrolled ongoing illness, for example: thrombotic or hemorrhagic disorders; hemoptysis; ongoing infection requiring systemic antibiotic treatment; congestive heart failure, angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months; stroke, transient ischemic attack (TIA), or other grade 3-4 arterial thromboembolic event occurring within 6 months; uncontrolled hypertension (≥150/≥90 millimeters of mercury [mmHg]); cardiac arrhythmia that requires treatment or asymptomatic sustained ventricular tachycardia; peripheral neuropathy ≥Grade 2; human immunodeficiency virus (HIV) or active, uncontrolled hepatitis, liver cirrhosis at a level of Child-Pugh Class B (or worse), liver cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. (Clinically meaningful ascites is defined as ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis)
- •Has a serious or nonhealing wound, ulcer, or bone fracture within 28 days before study entry
- •Has experienced any Grade 3 or 4 gastrointestinal bleeding within 3 months before study entry
- •Has a history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess <6 months before randomization, or the participant has a history of poorly controlled or recurrent inflammatory bowel disease (including Crohn's disease or ulcerative colitis)
- •Has participated in a clinical study of a non-approved experimental agent or procedure within 4 weeks prior to study entry for small molecules, or 8 weeks before study entry for non-approved monoclonal antibodies
- •Has a known allergy to ramucirumab or its excipients, a monoclonal antibody (MAb), or any other therapeutic protein, such as fresh frozen plasma, human serum albumin (HSA), cytokines, or interleukins. If there is suspicion that the participant may have an allergy, the participant should be excluded
- •Is pregnant (confirmed by urine or serum pregnancy test) or lactating
- •Has known alcohol or drug dependency
- •Is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs)
- •Is not considered to be suitable for this study, in the opinion of the investigator
研究组 & 干预措施
Ramucirumab
Ramucirumab administered intravenously (IV) at escalating doses (6 milligrams per kilogram [mg/kg] up to 10 mg/kg) every 2-3 weeks for 6 weeks (1 Cycle). Treatment may continue until discontinuation criterion is met.
干预措施: Ramucirumab (Biological)
结局指标
主要结局
Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious Adverse Events (SAEs)
时间窗: Baseline through Study Completion (Up to 12 Weeks)
A summary of AEs and SAEs considered by the investigator to be drug-related is located in the Reported Adverse Events module. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.
Pharmacokinetics: Maximum Concentration (Cmax) of Ramucirumab
时间窗: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
Pharmacokinetics: Minimum Concentration (Cmin) of Ramucirumab
时间窗: Cycle 2-5: Predose
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
时间窗: Cycle 1 & 2: Predose, End of Infusion, 0.5 hour (h) ,1h, 2h, 4h, 8h, 24h, 48h,72h or 96h, 168h, 264h, and 336h Postdose (and 504h Postdose Cohort 2 only)
Cycle 1 analysis performed: Area Under the Concentration-Time Curve Zero to Infinity (AUC\[0-∞\]); Cycle 2 analysis performed: Area Under the Concentration-Time Curve Over the Dosing Interval at Steady State (AUC\[τ,ss\])
次要结局
- Duration of Stable Disease (SD)(Baseline to Progressive Disease or Death Due to Any Cause (Up to 10 Weeks))
- Time to Disease Progression(Baseline to Progressive Disease (Up to 10 Weeks))
- Duration of Response(Time Between Meeting Response Criteria and Progressive Disease or Death Due to Any Cause (Up to 10 Weeks))
- Number of Participants With Anti-Ramucirumab Antibodies(Cycle 1: Pre-infusion, Cycle 2: Pre-infusion, Cycle 3: Pre-infusion)
- Number of Participants With Best Objective Response (BOR)(Baseline to Progressive Disease or Participant Stopped Study (Up to 10 Weeks))