A Phase 1, Nonrandomized, Open-Label Investigation of Subcutaneous Ramucirumab Administration in Participants With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab
研究概览
简要总结
The purpose of this study in participants with advanced cancer is to learn more about the safety of ramucirumab when given by injection under the skin (subcutaneous injection). The study will also measure how much ramucirumab gets into the bloodstream 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
- •Have evaluable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
- •In the judgment of the investigator, be an appropriate candidate for experimental therapy and:
- •For Cohort A only: Have exhausted all anticancer treatments with proven clinical benefit OR
- •For Cohorts B and C only: Must have one of the three conditions below:
- •Have exhausted all anti-cancer treatments with proven clinical benefit, OR
- •Have hepatocellular carcinoma or gastric cancer who have received prior treatment, and where IV ramucirumab monotherapy is clinically acceptable treatment after progression OR
- •Have a diagnosis for which IV ramucirumab in combination with additional anticancer therapy is clinically acceptable treatment
- •Additionally, it must be clinically acceptable to delay initiation of the combination partner for 3 weeks from the initiation of ramucirumab dosing.
- •Eastern Cooperative Oncology Group performance status score of 0 or
- •Have discontinued all previous treatments for cancer with adequate wash-out period and recovered from the acute effects of therapy.
- •Have adequate hematologic, hepatic, and renal functions and electrolytes.
- •Males and females of child-bearing potential must agree to use highly effective contraceptive methods during study treatment and for at least 84 days/12 weeks following the last dose of study drug.
排除标准
- •Have uncontrolled hypertension defined as systolic blood pressure (BP) >150 mmHg or diastolic BP >90 mmHg despite standard medical management.
- •Have significant bleeding disorders or experienced Grade 3/4 gastrointestinal (GI) bleeding within 3 months prior to enrollment.
- •Have hepatic impairment (such as severe liver cirrhosis Child-Pugh B [or worse], cirrhosis with a history of hepatic encephalopathy, clinically meaningful ascites requiring ongoing treatment with diuretics and/or paracentesis, or history of hepatorenal syndrome).
- •Have experienced any arterial thromboembolic events (ATEs), including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, ≤6 months prior to randomization.
- •The participant has clinically relevant congestive heart failure (CHF; New York Heart Association [NYHA] Grade ≥2) or symptomatic or poorly controlled cardiac arrhythmia.
- •Have symptomatic central nervous system (CNS) metastases. Screening is not required.
- •Have history of GI perforation and/or fistula within 6 months prior to enrollment.
- •Have an active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing uncontrolled intercurrent illness.
- •Have a serious or non-healing wound, ulcer, or bone fracture within 4 weeks prior to enrollment.
- •Have received IV ramucirumab in the past.
研究组 & 干预措施
Ramucirumab
Participants received starting dose of 700 milligram (mg) ramucirumab loading dose (LD) subcutaneously (SC) followed, a week later, by 350 mg ramucirumab maintenance dose (MD) administered SC once a week.
干预措施: Ramucirumab (Drug)
结局指标
主要结局
Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of Ramucirumab
时间窗: Cycle (C) 1 Day (D) 1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose
PK: AUC of Ramucirumab over the dosing interval was evaluated. Cycle = 21 days.
PK: Maximum Concentration (Cmax) of Ramucirumab
时间窗: C1D1:Predose; C1D2:24 hours (h) postdose;C1D4:48-96 h postdose;C1D8:predose;C1D15:predose;C1D18:48-96 h postdose;C2D1:predose;C2D8:predose;C2D11:48-96h postdose;C3D1:predose
PK: Cmax of Ramucirumab was evaluated.
PK: Serum Trough Concentration (Ctrough) of Ramucirumab
时间窗: C1D8: predose; C1D15: predose; C2D1: predose; C2D8: predose; C3D1: predose
Ctrough of Ramucirumab was evaluated.
次要结局
- Percentage of Participants With Anti-Ramucirumab Antibodies(C1D1: predose; C1D15: predose; C2D8: predose; C4D1: predose)
- Number of Participants With Injection Site Reactions (ISRs)(Cycle 1, Cycle 2, Cycle 3: D1, D8, D15, D22: 5-15 min, 60 min post injection; C1D2: 24 hours (h) post injection; C1D4 (± 1 day))