A Phase 2, Open-label Study of IMC-1121B in Combination With Paclitaxel and Carboplatin as First-line Therapy in Patients With Stage IIIB/IV Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Are Progression-free (PFS) at 6 Months
研究概览
简要总结
The purpose of this study is to evaluate the progression-free survival (PFS) rate at 6 months of ramucirumab administered in combination with paclitaxel and carboplatin as first-line therapy for Stage IIIB or IV non-small cell lung cancer
详细描述
Non-small cell lung cancer (NSCLC) accounts for 75-80% of all lung cancers. The advanced stages are associated with poor survival rates, a median survival rate of approximately 3.9 months if left untreated.
Angiogenesis is a process for wound healing and restoring blood flow to tissues after injury. It is the physiological process involving the growth of new blood vessels from pre-existing vessels. Angiogenesis may be promoted by growth factors and in diseases such as cancer, where growth factors are over expressed, the body loses the ability to maintain a balanced angiogenesis. This may embellish the existing supplies of blood; potentially increasing the delivery of oxygen and nutrients supplies for cancer growth and survival.
Ramucirumab is an angiogenesis inhibitor; and is believed to block the promotion of the growth factor to form new blood vessels, thus reducing the blood supply to the cancer cells.
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
- •Histologically or cytologically confirmed NSCLC
- •Advanced NSCLC
- •Measurable disease (as defined by Response Evaluation Criteria in Solid Tumors [RECIST 1.0])
- •Eastern Cooperative Oncology Group (ECOG) Performance Status is ≤ 1
- •Age ≥ 18 years
- •Adequate hematologic function = an absolute neutrophil count (ANC) ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and a platelet count ≥ 100,000/microliter (μL)
- •Adequate hepatic function = a total bilirubin ≤ 1.5 mg/dL transaminases and alkaline phosphatase ≤ 5 x the upper limit of normal (ULN)
- •Adequate renal function serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) > 60 mL/minute, and urine dipstick for protein < 1+ (ie, either 0 or trace)
- •Adequate coagulation function, INR ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 5 seconds above ULN
- •Adequate contraception
- •Signed informed consent
排除标准
- •Untreated CNS metastases
- •Prior bevacizumab therapy
- •Radiologically documented evidence of major blood vessel invasion or encasement by cancer
- •Prior systemic chemotherapy for Stage IIIB/IV NSCLC
- •Prior systemic chemotherapy or radiation therapy for Stage I-IIIA NSCLC < 1 year prior
- •Any concurrent malignancy other than basal cell skin cancer, or carcinoma in situ of the cervix
- •Concurrent treatment with other anticancer therapy, including other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, chemoembolization, or targeted therapy
- •Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Uncontrolled thrombotic or hemorrhagic disorders
- •Poorly-controlled hypertension
- •Chronic daily treatment with aspirin (> 325 mg/day) or other known inhibitors of platelet function
- •History of gross hemoptysis (defined as bright red blood or ≥ 1/2 teaspoon)
- •Serious non-healing wound, ulcer, or bone fracture
- •Undergone major surgery or subcutaneous venous access device placement. Post-operative bleeding complications or wound complications from a surgical procedures performed in the last 2 months
- •Elective or a planned major surgery to be performed during the course of the trial
- •Peripheral neuropathy ≥ Grade 2 (National Cancer Institute Common Toxicity Criteria for Adverse Events, Version 3.0 [NCI-CTCAE v 3.0])
- •If female, is pregnant or lactating
- •Radiographic evidence of intratumor cavitation
- •Grade 3-4 gastrointestinal bleeding within 3 months prior to study entry
研究组 & 干预措施
ramucirumab + paclitaxel + carboplatin
Participants will receive ramucirumab in combination with paclitaxel and carboplatin until disease progression, the development of an unacceptable toxicity, or other withdrawal criteria, for up to six cycles (3 weeks per cycle).
In the absence of any withdrawal criteria, participants will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit upon review every 6 weeks.
干预措施: Ramucirumab (Biological)
ramucirumab + paclitaxel + carboplatin
Participants will receive ramucirumab in combination with paclitaxel and carboplatin until disease progression, the development of an unacceptable toxicity, or other withdrawal criteria, for up to six cycles (3 weeks per cycle).
In the absence of any withdrawal criteria, participants will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit upon review every 6 weeks.
干预措施: Paclitaxel (Drug)
ramucirumab + paclitaxel + carboplatin
Participants will receive ramucirumab in combination with paclitaxel and carboplatin until disease progression, the development of an unacceptable toxicity, or other withdrawal criteria, for up to six cycles (3 weeks per cycle).
In the absence of any withdrawal criteria, participants will continue to receive ramucirumab monotherapy every 3 weeks, provided there is ongoing evidence of benefit upon review every 6 weeks.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Percentage of Participants Who Are Progression-free (PFS) at 6 Months
时间窗: 6 months
Data presented are the percentage of participants without disease progression or death at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progressive disease was defined as having at least a 20% increase in sum of longest diameter of target lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
次要结局
- Summary of Participants Reporting Adverse Events(Baseline up to 32.5 months)
- Duration of Response(First dose up to 32.5 months)
- Overall Survival (OS) at 1 Year(First dose to 1 year)
- Progression-free Survival (PFS)(First dose to measured progressive disease or death due to any cause, up to 32.5 months)
- Maximum Concentration of Ramucirumab (Cmax)(Week 18 (Cycle 6), at 1-Hour Post End of Infusion)
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])(First dose to measured progressive disease or death due to any cause up to 32.5 months)
- Overall Survival (OS)(First dose to death due to any cause, up to 32.5 months)
- Serum Anti-Ramucirumab Antibody Assessment(Week 15 (Cycle 5))