A Clinical Trial of the Safety and Efficacy of ABX-EGF in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil in Subjects With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 43
- 主要终点
- Number of Participants With Grade 3 or Grade 4 Diarrhea (Part 2)
研究概览
简要总结
The purpose of this study is to determine if panitumumab, in combination with irinotecan, leucovorin, and 5-fluorouracil (5-FU) is safe and efficacious in patients with metastatic colorectal cancer.
详细描述
Indication Metastatic Colorectal Cancer Primary Objective To assess the safety of ABX-EGF in combination with the FOLFIRI regimen in subjects with metastatic colorectal cancer. (The primary objective in the original protocol was to assess progression free survival after treatment with ABX-EGF in combination with the Saltz regimen in subjects with metastatic colorectal cancer).
Secondary Objective(s) To assess the clinical efficacy of ABX-EGF in combination with the FOLFIRI regimen in subjects with metastatic colorectal cancer. (Secondary objectives in the original protocol were to assess safety and additional measures of the clinical efficacy of ABX-EGF in combination with the Saltz regimen in subjects with metastatic colorectal cancer).
To assess the pharmacokinetics (PK) of ABX-EGF in combination with the FOLFIRI regimen in subjects with metastatic colorectal cancer. (Secondary objectives in the original protocol were to assess the PK of ABX-EGF in combination with the Saltz regimen, and the PK of irinotecan (IR) and its active metabolite SN-38 when IR is given in combination with ABX-EGF, leucovorin (LV), and 5-fluorouracil (5-FU) in subjects with metastatic colorectal cancer)
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
- •Able to comprehend and sign an Institutional Review Board (IRB)-approved informed consent form
- •Pathologic diagnosis of colorectal cancer - Metastatic colorectal adenocarcinoma
- •If history of adjuvant chemotherapy for colorectal cancer, must have been free of disease for greater than or equal to 1 year after completion of adjuvant chemotherapy
- •Unidimensionally measurable disease
- •Paraffin-embedded tumor tissue available for immunohistochemistry studies of epidermal growth factor receptor (EGFr) expression (archived tissue is acceptable)
- •Tumor over-expressing EGFr by immunohistochemistry (staining must be the sum of 1+, 2+ and 3+ in greater than or equal to 10% of evaluated tumor cells; staining and evaluation to be conducted at a central laboratory)
- •Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1
- •Adequate hematologic, renal, and hepatic function
排除标准
- •Female (of childbearing potential, post-menopausal for less than 6 months, not surgically sterilized, or not abstinent) not consenting to use adequate contraceptive precautions during the course of the study and for 6 months after the last ABX-EGF infusion
- •Female who is breast-feeding or pregnant
- •Any kind of disorder that compromises the ability of the patient to give written informed consent and/or comply with the study procedures
- •History of any chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation or study drug administration or may interfere with compliance or the interpretation of study results
- •Untreated brain metastases
- •Therapy for colorectal cancer other than surgery and 5-FU-based adjuvant therapy
- •Prior treatment for metastatic colorectal cancer
- •Prior irinotecan
- •Prior or concurrent radiation therapy for colorectal cancer, including prior adjuvant radiation therapy to the pelvis
- •Known allergy to irinotecan, 5-fluorouracil, or leucovorin
- •Known Gilbert's disease
- •Known dihydropyrimidine dehydrogenase (DPD) deficiency
- •Prior EGFr-targeting agents
- •Use of investigational therapy used with adjuvant intent within 30 days before the first ABX-EGF infusion
- •If prior history of cancer other than colorectal carcinoma, basal cell carcinoma, or cervical carcinoma in situ, no treatment or active disease within 5 years
- •Active inflammatory bowel disease or other bowel disease (other than colorectal carcinoma) causing chronic diarrhea (defined as greater than 4 stools per day)
- •Partial or complete bowel obstruction, known chronic malabsorption, total colectomy, or other major abdominal surgery that might result in substantial alteration in transit to absorption of oral medication
- •Ascites or pleural effusion requiring therapeutic paracentesis or thoracentesis; subject with small, stable, asymptomatic pleural effusions or ascites may be enrolled; subject who has been rendered asymptomatic by successful sclerosis of an effusion may be enrolled.
- •Active interstitial pneumonia or interstitial fibrosis
- •Left ventricular ejection fraction (LVEF) less than 45%, as measured by multiple-gated acquisition (MUGA) scan - Myocardial infarction within 1 year before the first ABX-EGF infusion
- •Any of the following within 6 months before the first study drug dose:
- •Unstable angina;
- •Symptomatic congestive heart failure;
- •Serious uncontrolled cardiac arrhythmia;
- •Cerebrovascular accident or transient ischemic attack;
- •Pulmonary embolism;
- •Deep vein thrombosis;
- •Other significant thromboembolic event.
- •Subject known to be human immunodeficiency virus (HIV) positive
- •History of any chronic medical or psychiatric condition or laboratory abnormality that, in the opinion of the Investigator, may increase the risks associated with study participation or study drug administration or may interfere with patient compliance or the interpretation of study results
- •Unwilling or unable to comply with study requirements
- •Known allergy to the ingredients of the study drug or to Staphylococcus protein A
研究组 & 干预措施
Part 1: Panitumumab + IFL
Panitumumab (2.5 mg/kg once weekly for up to 48 weeks or until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan, 5-fluorouracil (5-FU)and leucovorin (IFL chemotherapy regimen)
干预措施: Irinotecan (Drug)
Part 1: Panitumumab + IFL
Panitumumab (2.5 mg/kg once weekly for up to 48 weeks or until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan, 5-fluorouracil (5-FU)and leucovorin (IFL chemotherapy regimen)
干预措施: Panitumumab (Biological)
Part 1: Panitumumab + IFL
Panitumumab (2.5 mg/kg once weekly for up to 48 weeks or until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan, 5-fluorouracil (5-FU)and leucovorin (IFL chemotherapy regimen)
干预措施: 5-Fluorouracil (Drug)
Part 1: Panitumumab + IFL
Panitumumab (2.5 mg/kg once weekly for up to 48 weeks or until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan, 5-fluorouracil (5-FU)and leucovorin (IFL chemotherapy regimen)
干预措施: Leucovorin (Drug)
Part 2: Panitumumab + FOLFIRI
Panitumumab (2.5 mg/kg once weekly until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan/5-FU/leucovorin chemotherapy (the FOLFIRI regimen)
干预措施: Irinotecan (Drug)
Part 2: Panitumumab + FOLFIRI
Panitumumab (2.5 mg/kg once weekly until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan/5-FU/leucovorin chemotherapy (the FOLFIRI regimen)
干预措施: Panitumumab (Biological)
Part 2: Panitumumab + FOLFIRI
Panitumumab (2.5 mg/kg once weekly until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan/5-FU/leucovorin chemotherapy (the FOLFIRI regimen)
干预措施: 5-Fluorouracil (Drug)
Part 2: Panitumumab + FOLFIRI
Panitumumab (2.5 mg/kg once weekly until disease progression, intolerable adverse event or other reason for discontinuation) in combination with irinotecan/5-FU/leucovorin chemotherapy (the FOLFIRI regimen)
干预措施: Leucovorin (Drug)
结局指标
主要结局
Number of Participants With Grade 3 or Grade 4 Diarrhea (Part 2)
时间窗: Until disease progression (median 47 weeks)
The number of participants with grade 3 or grade 4 diarrhea in Part 2 of the study. Grading of diarrhea followed the grading scale in Version 2.0 of the National Cancer Institute Common Toxicity Criteria (NCI CTC).
Number of Participants With Grade 3 or Grade 4 Diarrhea (Part 1)
时间窗: Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first
The number of participants with grade 3 or grade 4 diarrhea in Part 1 of the study. Grading of diarrhea followed the grading scale in Version 2.0 of the National Cancer Institute Common Toxicity Criteria (NCI CTC).
次要结局
- Number of Participants With an Objective Tumor Response (Part 2)(Until disease progression (median 47 weeks))
- Time to Disease Progression (Part 2)(From enrollment until death or diease progression. Maximum follow-up time was 16 months.)
- Progression-free Survival Time (Part 2)(From enrollment until disease progression or death. Maximum follow-up time was 16 months.)
- Progression-free Survival Time (Part 1)(From enrollment until disease progression or death. Maximum follow-up time was 25 months.)
- Survival Time (Part 2)(From enrollment until death. Maximum follow-up time was 16 months.)
- Number of Participants Who Died (Part 2)(From enrollment until last contact. Maximum follow-up was 16 months.)
- Number of Participants With Objective Tumor Response (Part 1)(Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first)
- Time to Disease Progression (Part 1)(From enrollment until disease progression or death. Maximum follow-up time was 25 months.)
- Survival Time (Part 1)(From enrollment until death. Maximum follow-up time was 25 months.)
- Time to Treatment Failure (Part 1)(Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first)
- Time to Initial Objective Tumor Response (Part 1)(Until disease progression (median 35 weeks) or 48 weeks, whichever occurred first)