A Phase I/II Trial of Pertuzumab in Combination With Cetuximab and Irinotecan in Previously Treated Metastatic Colorectal Cancer

National Cancer Institute (NCI)1 个研究点分布在 1 个国家目标入组 17 人开始时间: 2007年10月最近更新: 2015年3月31日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 17
试验地点: 1
主要终点: Recommended Phase II Dose of Pertuzumab When Administered in Combination With Cetuximab (Phase I)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Monoclonal antibodies, such as pertuzumab and cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pertuzumab together with cetuximab may kill more tumor cells. This phase I/II trial is studying the side effects and best dose of pertuzumab when given together with cetuximab and to see how well they work in treating patients with previously treated locally advanced or metastatic colorectal cancer

详细描述

PRIMARY OBJECTIVES:

I. To determine the safety, tolerability, and recommended phase II dose of pertuzumab when administered in combination with cetuximab in patients with cetuximab-refractory locally advanced or metastatic colorectal cancer.

II. To evaluate the objective tumor response rate (RR) in patients treated with this regimen.

SECONDARY OBJECTIVES:

I. To evaluate the median progression-free survival (PFS) of patients treated with this regimen.

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

•Patients with a history of colorectal cancer (CRC) treated by surgical resection and who develop radiological or clinical evidence of metastatic disease do not require separate histological or cytological confirmation of metastatic disease unless 1 of the following criteria are met:
•More than 5 years has elapsed between the primary surgery and the development of metastatic disease
•The primary cancer was stage I
•Patients must have representative tumor specimens in paraffin blocks or at least 15 unstained slides with an associated pathology report obtained at any time prior to study entry:
•Cytology specimens are not acceptable replacements
•Patients must have their tumor tissue screened for KRAS mutation status, and be found to have a KRAS wild-type tumor:
•No KRAS-mutated tumor
•Locally advanced or metastatic disease
•Not curable by surgery or amenable to radiotherapy with curative intent
•Must have received an cetuximab-containing regimen for at least 6 weeks for treatment of metastatic disease
•Documented progression of disease or intolerable toxicity during or within 3 months of receiving this regimen
•Patients who have received an cetuximab-containing regimen as adjuvant therapy for resected stage II or III CRC are eligible provided recurrent disease is documented < 6 months after completion of adjuvant treatment
•Must have received >= 1 prior chemotherapeutic regimen for treatment of metastatic disease with any of the following:
•Cetuximab
•Must have resolution of any skin rash related to prior treatment with cetuximab
•No prior cetuximab which required a dose reduction for toxicity
•5-fluorouracil or capecitabine
•Irinotecan hydrochloride or oxaliplatin
•Measurable disease by CT scan or physical exam
•ECOG performance status (PS) 0-1 (Karnofsky PS 70-100%)
•Life expectancy > 12 weeks
•Absolute neutrophil count >= 1,500/mcL
•Platelet count >= 100,000/mcL
•Leukocytes >= 3,000/mcL
•Hemoglobin >= 9 g/dL (transfusion, erythropoietin, or other approved hematopoietic growth factors allowed)
•Total bilirubin =< 1.5 times upper limit of normal (ULN)
•AST and ALT =< 5 times ULN
•Creatinine normal OR Creatinine clearance >= 60 mL/min
•Not pregnant or nursing
•Negative pregnancy test
•Fertile patients must use effective contraception prior to and during study therapy
•Cardiac left ventricular ejection fraction >= 50% OR >= lower limit of normal
•No evidence of left ventricular wall motion abnormalities as measured by ECHO or MUGA scan
•None of the following cardiac conditions:
•Uncontrolled high blood pressure
•Unstable angina
•Symptomatic congestive heart failure
•Congestive heart failure, cardiac dysfunction, or cardiomyopathy requiring medication treatment
•Myocardial infarction within the past 6 months
•Serious uncontrolled cardiac arrhythmia
•New York Heart Association class III or IV heart disease
•No active or uncontrolled infection
•No predisposing colonic or small bowel disorders in which the symptoms are uncontrolled as indicated by baseline pattern of > 3 loose stools/day (in patients without a colostomy or ileostomy)
•Patients with a colostomy or ileostomy may be eligible at investigator discretion
•No psychiatric illness/social situation that would limit compliance with study requirements
•No other prior or concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ carcinoma of the cervix, lobular carcinoma in situ in one breast, or other cancer from which the patient has been disease-free for at least 5 years
•No other medical or psychiatric disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the study results or render the patient at high risk for treatment complications
•No history of allergic reactions, hypersensitivity, or intolerance to cetuximab, and/or compounds of similar chemical or biologic composition to pertuzumab or cetuximab (i.e., other monoclonal antibodies such as bevacizumab) that led to discontinuation of the drug
•Patients able to tolerate subsequent infusions after a reaction are eligible
•At least 4 weeks since prior major surgery (e.g., laparotomy) and recovered (Insertion of a vascular access device is not considered major or minor surgery)
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排除标准

未提供

研究组 & 干预措施

Arm I

Experimental

Phase I: Patients receive pertuzumab IV over 30-60 minutes on day 1. Patients also receive cetuximab IV over 60-120 minutes on days 2, 8, and 15 of course 1 and on days 1, 8, and 15 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.