Randomized, Open Label, Stratified Phase 2 Trial of Gemcitabine, Carboplatin, and Cetuximab With Vs. Without IMC-A12 in Chemotherapy-Naive Patients With Advanced/Metastatic Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
研究概览
简要总结
The purpose of this study is to determine the number of participants whose cancer shrinks or disappears after treatment on the study.
详细描述
Participants with Stage IIIb or IV non-small cell lung cancer (NSCLC) who have not received previous chemotherapy will be stratified, based on disease histology (squamous versus [vs.] nonsquamous).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Has histologically or cytologically confirmed, Stage IIIb - IV NSCLC
- •Has metastatic disease
- •Has a tumor measurable according to Response Evaluation Criteria in Solid Tumors (RECIST)
- •Has adequate hematologic function
- •Has adequate hepatic function
- •Has adequate renal function
- •Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation
排除标准
- •Has uncontrolled brain metastases
- •Has leptomeningeal disease
- •Has received previous chemotherapy for NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 6 months prior to randomization)
- •Receiving any other investigational agent(s)
- •Has a history of treatment with other agents targeting the insulin-like growth factor (IGF) or the epidermal growth factor (EGF) receptor
- •Has a known allergy / history of hypersensitivity reaction to any of the treatment components
- •Has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range [fasting glucose <160 milligrams per deciliter (mg/dL) or below the upper limit of normal (ULN) and hemoglobin A1C≤ 7%] and that they are on a stable dietary or therapeutic regimen for this condition
- •Has an uncontrolled intercurrent illness
- •Pregnant or lactating
- •Has a history of another primary cancer, with the exception of: a) curatively resected nonmelanomatous skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor treated with curative intent and no known active disease present and no treatment administered during the last 3 years
- •Has superior vena cava syndrome contraindicating hydration
- •Has current clinically-relevant coronary artery disease (New York Heart Association III or IV) or uncontrolled congestive heart failure
- •Has any National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version (v) 3.0 Grade ≥2 peripheral neuropathy
- •Has significant third space fluid retention, requiring repeated drainage
研究组 & 干预措施
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Gemcitabine (Drug)
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Cisplatin (Drug)
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: IMC-A12 (cixutumumab) (Biological)
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Cetuximab (Biological)
GCiC + IMC-A12 (Gemcitabine/Cisplatin/Cetuximab + Cixutumumab)
Cycles repeat every 3 weeks for first 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. Gemcitabine/Carboplatin/Cetuximab (GCC) plus cixutumumab will change to Gemcitabine/Cisplatin/Cetuximab (GCiC) plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Carboplatin (Drug)
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Gemcitabine (Drug)
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Cisplatin (Drug)
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Cetuximab (Biological)
GCiC (Gemcitabine/Cisplatin/Cetuximab)
Cycles repeat every 3 weeks for 6 cycles (18 weeks) and then once every 2 weeks (maintenance therapy) until disease progression, intolerable toxicity, withdrawal of consent or other withdrawal criteria met
*Cisplatin will replace Carboplatin. GCC plus cixutumumab will change to GCiC plus cixutumumab (participants enrolled subsequent to this change will receive gemcitabine, cisplatin and cetuximab, plus cixutumumab)
干预措施: Carboplatin (Drug)
结局指标
主要结局
Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
时间窗: Randomization to measured progressive disease (PD) (up to 16.9 months)
ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated \* 100.
次要结局
- Cmax of Cixutumumab for Cycle 3(Week 7 (Cycle 3, Day 1))
- Maximum Concentration (Cmax) of Cixutumumab at Study Day 1(Day 1)
- Progression-Free Survival (PFS)(Randomization to PD or death due to any cause or censor (up to 16.9 months))
- Duration of Response(Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months))
- Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)(Prior to first infusions of Cycles 1, 3, and 5 and 30 days following the end of therapy)
- Cmin of Cixutumumab for Cycle 3(Week 7 (Cycle 3, Day 1))
- Overall Survival (OS)(Randomization to death due to any cause or censor (up to 30.4 months))
- Number of Participants With Adverse Events (AEs) or Deaths(Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up)
- Cmax of Cixutumumab for Cycle 1(Week 1 (Cycle 1, Day 1))
- Cmax of Cixutumumab Cycle 5(Week 13 (Cycle 5, Day 1))
- Minimum Concentration (Cmin) of Cixutumumab at Study Day 1(Day 1)
- Cmin of Cixutumumab for Cycle 5(Week 13 (Cycle 5, Day 1))
- Time To Progression (TTP)(Randomization to months until PD or censor (up to 16.9 months))
- Cmin of Cixutumumab for Cycle 1(Week 1 (Cycle 1, Day 1))