NCT00845039终止2 期
A Randomized Phase II Clinical Trial Investigating Irinotecan Plus Cetuximab With or Without Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody (IMC-A12) for the Treatment of Patients With Metastatic K-Ras Wild Type Carcinoma of the Colon or Rectum That Has Progressed on Oxaliplatin and Bevacizumab Given as First-Line Therapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS) Rate at 18 Weeks
研究概览
简要总结
The purpose of this study is to determine the value of adding IMC-A12 to irinotecan and cetuximab in participants with metastatic colorectal cancer (CRC).
详细描述
The purpose of this study is to determine the value of adding IMC-A12 to irinotecan + cetuximab in improving progression-free survival (PFS) at 18 weeks from the date of randomization for participants with metastatic Kirsten Rat Sarcoma (K-RAS) wild-type CRC that has progressed on an oxaliplatin/bevacizumab-containing regimen.
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
- •Must consent to be in the study and must have signed and dated Institutional Review Board (IRB)-approved consent forms conforming to federal and institutional guidelines for the pre-entry tumor sample submission for central K-RAS testing and for the study treatment
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- •Must have metastatic CRC
- •The CRC tumor or metastatic tumor must be v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog gene (K-RAS) wild-type as determined by central testing
- •Must be documented disease progression during first-line therapy containing both oxaliplatin and bevacizumab
- •Most recent treatment regimen must have ended ≥21 days prior to randomization, and clinically significant side effects associated with previous therapy must have resolved to ≤Grade 1 with the exception of neuropathy which must have resolved to ≤Grade 2
- •Imaging of the chest, abdomen and pelvis with computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 3 weeks prior to randomization
- •Must have measurable disease, defined as at least 1 lesion outside a previous radiation therapy (RT) field that can be accurately measured in at least 1 dimension as ≥20 millimeters (mm) with conventional techniques or as ≥10mm with 5mm cuts using a spiral CT scan
- •Evidence of adequate bone marrow function: absolute neutrophil (ANC) ≥1200 cubed millimeters (mm³), hemoglobin ≥9 grams per deciliter (g/dL), platelets ≥100,000 mm³
- •Evidence of adequate hepatic function. If no liver metastases: aspartate aminotransferase (AST) ≤2.5 times (x) upper limit of normal (ULN), total bilirubin ≤1.5 x ULN for the lab. In the presence of liver metastases: AST ≤5.0 x ULN, total bilirubin ≤1.5 x ULN for the lab
- •Serum creatinine must be ≤1.5 x ULN for the lab
- •Must have a fasting blood glucose <126 milligrams/deciliter (mg/dL). Fasting is defined as no caloric intake for at least 8 hours
排除标准
- •Life expectancy less than 12 weeks
- •Diagnosis of anal or small bowel carcinoma
- •Tumor that is considered by the surgeon to be amenable to complete resection
- •Previous RT to >25% of bone marrow
- •RT to sites of measurable disease chosen as target lesions
- •Radiological evidence and/or clinical signs or symptoms of central nervous system (CNS) metastases
- •Any of the following conditions and events: uncontrolled hypertension, defined as systolic blood pressure (BP) >150 millimeters of mercury (mmHg) or diastolic BP >100 mmHg with or without antihypertensive medication (participants with hypertension that is well-controlled on medication are eligible); unstable angina within 6 months before randomization; New York Heart Association (NYHA) Class III or IV cardiac disease; myocardial infarction (MI) within 6 months before randomization; symptomatic arrhythmia; CNS cerebrovascular ischemia [transient ischemic attack (TIA) or stroke] within 6 months before randomization
- •Other malignancies unless the participant is considered to be disease-free and has completed therapy for the malignancy ≥12 months prior to randomization. Participants with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin
- •Serious or non-healing wound, skin ulcers, or bone fracture
- •Any significant bleeding unless the source of bleeding has been resected
- •History of bleeding diathesis or coagulopathy (participants on stable anticoagulant therapy are eligible)
- •Any evidence of active infection
- •Active inflammatory bowel disease
- •Grade 3 or 4 diabetes mellitus as defined by National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 pancreatic endocrine: glucose intolerance (participants with diabetes controlled with diet and/or oral medications are eligible)
- •Symptomatic interstitial pneumonitis or definitive evidence of interstitial pneumonitis described on CT scan or chest x-ray in asymptomatic participants
- •Any other serious concomitant medical condition that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to participate in the study
- •Previous hypersensitivity reaction to monoclonal antibodies
- •Previous treatment with irinotecan, cetuximab, or any agent specifically targeting insulin-like growth factor (IGF) receptors
- •Treatment with an investigational drug within 30 days prior to randomization
- •Pregnancy or lactation at the time of participant entry
- •Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the participant from meeting the study requirements
研究组 & 干预措施
Cetuximab + Irinotecan
Active Comparator
Participants in Treatment Group 1 will receive intravenous infusions of Cetuximab 500 milligrams per square meter (mg/m²) and Irinotecan 180 mg/m².
干预措施: Cetuximab (Biological)
Cetuximab + Irinotecan
Active Comparator
Participants in Treatment Group 1 will receive intravenous infusions of Cetuximab 500 milligrams per square meter (mg/m²) and Irinotecan 180 mg/m².
干预措施: Irinotecan (Drug)
Cetuximab + IMC-A12 + Irinotecan
Experimental
Participants in Treatment Group 2 will receive intravenous infusions of Cetuximab 500 mg/m², IMC-A12 10 milligrams/kilogram (mg/kg) and Irinotecan 180 mg/m².
干预措施: Cetuximab (Biological)
Cetuximab + IMC-A12 + Irinotecan
Experimental
Participants in Treatment Group 2 will receive intravenous infusions of Cetuximab 500 mg/m², IMC-A12 10 milligrams/kilogram (mg/kg) and Irinotecan 180 mg/m².
干预措施: Irinotecan (Drug)
Cetuximab + IMC-A12 + Irinotecan
Experimental
Participants in Treatment Group 2 will receive intravenous infusions of Cetuximab 500 mg/m², IMC-A12 10 milligrams/kilogram (mg/kg) and Irinotecan 180 mg/m².
干预措施: IMC-A12 (cixutumumab) (Biological)
结局指标
主要结局
Progression-Free Survival (PFS) Rate at 18 Weeks
时间窗: Approximately 18 Weeks
次要结局
- Toxicity of the Irinotecan + Cetuximab + IMC-A12 Regimen(Randomization up to 26.3 months)
- Progression Free Survival (PFS) Over Entire Duration(Randomization up to 26.3 months)
- The Number of Participants Who Had a Complete Resection/Ablation of Metastases With no Evidence of Disease Remaining (Resection Rate)(Randomization up to 26.3 months)
- Change in Behavioral and Health Outcomes [BAHO] Quality of Life (QoL) Questionnaire(Baseline, after Cycle 3 (14-day cycle), study discontinuation 30-day follow-up (up to 26.3 months))
- Objective Response Rate (ORR) [Complete Response (CR) + Partial Response (PR)](Randomization up to 26.3 months)
- Overall Survival (OS)(Randomization up to 26.3 months)
- Post-treatment Serum Levels of IMC-A12 in Participants Receiving IMC-A12(Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks)
- Serum Anti-IMC-A12 Antibody Assessment(Prior to infusion at Cycles 1, 4, 7 (2-week cycles), and 4 to 6 weeks following discontinuation of treatment IMC-A12 up to 77 weeks)
研究者
研究点 (1)
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