PACCE: A Randomized, Open-Label, Controlled, Clinical Trial of Chemotherapy and Bevacizumab With and Without Panitumumab in the First-Line Treatment of Subjects With Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 1,053
- 主要终点
- Objective Tumor Response Through Week 12 (Irinotecan)
研究概览
简要总结
The purpose of this study is to assess whether treatment with the study drug, panitumumab given concomitantly with every 2 (Q2) week oxaliplatin-based chemotherapy and bevacizumab improves progression-free survival (PFS) compared to treatment Q2-week with oxaliplatin-based chemotherapy and bevacizumab alone. All subjects will receive Q2-week oxaliplatin- or irinotecan-based chemotherapy and bevacizumab. Control arm subjects will not receive concomitant panitumumab therapy.
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
- •Adenocarcinoma of the colon or rectum
- •Metastatic colorectal cancer (mCRC)
- •Measurable disease per modified response evaluation criteria in solid tumors (RECIST) criteria
- •ECOG performance status of 0 or 1
- •Available paraffin-embedded tumor tissue (from primary tumor or metastasis) or unstained slides of paraffin-embedded tissue
- •If history of other primary cancer, subject will be eligible only if she or he has:
- •Curatively resected non-melanomatous skin cancer;
- •Curatively treated cervical carcinoma in situ;
- •Other primary solid tumor curatively treated with no known active disease present and no treatment administered for the last 5 years.
- •Adequate hematologic data as follows:
- •Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9 cells/L;
- •Platelet count greater than or equal to 100 x 10^9/L;
- •Hemoglobin greater than or equal to 9.0 g/dL. - Adequate renal function:
- •Serum creatinine less than or equal to 1.5 x upper limit of normal (ULN);
- •Urinary protein dipstick of less than 2+ (if urinary dipstick 2+ or greater, then excretion of less than or equal to 1000 mg of protein per day as determined by 24-hour urine collection).
- •Adequate hepatic function:
- •Alkaline phosphatase less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
- •Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase)(AST) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
- •Alanine aminotransferase (serum glutamic-pyruvic transaminase) (ALT) less than or equal to 3 x ULN (if liver metastases, less than or equal to 5 x ULN);
- •Bilirubin less than or equal to 2 x ULN. - Competent to comprehend, sign, and date an IRB-approved informed consent form
- •Before any study-specific procedure, the appropriate written informed consent must be obtained.
排除标准
- •Prior chemotherapy or biologic (i.e., antibody or vaccine) treatment for mCRC disease - Last dose of adjuvant or radiosensitizing chemotherapy less than 6 months before randomization - Radiotherapy within 14 days before randomization
- •Elective and/or planned major surgical procedure to be performed during the course of this trial (surgery that arises as needed or necessary during the course of the study, not agreed a priori, will not make the subject ineligible)
- •Major surgery within 28 days before randomization
- •Central nervous system metastases
- •History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest X-ray or CT-scan
- •Clinically significant ascites
- •Preexisting bleeding diathesis or coagulopathy or the need for full-dose anticoagulation
- •Any of the following within 1 year before randomization:
- •Myocardial infarction;
- •Unstable angina;
- •Symptomatic congestive heart failure;
- •Serious uncontrolled cardiac arrhythmia;
- •Cerebrovascular accident or transient ischemic attack;
- •Gastrointestinal ulcer or hemorrhage;
- •Hemoptysis;
- •Pulmonary embolism;
- •Deep vein thrombosis, or other significant thromboembolic event.
- •Regular use of non-steroidal anti-inflammatory agents
- •Female subject of childbearing potential, not abstinent, and not willing to use contraceptives during the course of the study and for 6 months following the last dose of first-line treatment
- •Female subject who is breast-feeding or who has positive serum pregnancy test 72 hours prior to randomization
- •Male subject, not abstinent, and not willing to use adequate contraception upon enrollment into this study and for 6 months following the last dose of first-line treatment
- •Subject known to be human immunodeficiency virus (HIV) positive
- •Subject allergic to panitumumab or any components of panitumumab formulation
- •History of any 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 the conduct of the study or interpretation of study results
- •Subject unwilling or unable to comply with study requirements
- •Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
研究组 & 干预措施
Oxaliplatin and bevacizumab without panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone.
干预措施: Oxaliplatin Based Chemotherapy (Drug)
Oxaliplatin and bevacizumab without panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W alone.
干预措施: Bevacizumab (Drug)
Irinotecan and bevacizumab plus panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Panitumumab (Drug)
Irinotecan and bevacizumab plus panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Irinotecan Based Chemotherapy (Drug)
Irinotecan and bevacizumab plus panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Bevacizumab (Drug)
Irinotecan and bevacizumab without panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W alone
干预措施: Irinotecan Based Chemotherapy (Drug)
Irinotecan and bevacizumab without panitumumab
Irinotecan-based chemotherapy and Bevacizumab Q2W alone
干预措施: Bevacizumab (Drug)
Oxaliplatin and bevacizumab plus panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Oxaliplatin Based Chemotherapy (Drug)
Oxaliplatin and bevacizumab plus panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Panitumumab (Drug)
Oxaliplatin and bevacizumab plus panitumumab
Oxaliplatin-based chemotherapy and Bevacizumab Q2W plus panitumumab 6mg/kg Q2W
干预措施: Bevacizumab (Drug)
结局指标
主要结局
Objective Tumor Response Through Week 12 (Irinotecan)
时间窗: Overall Study
Objective tumor response (complete or partial) rate through week 12 based on central review in the Irinotecan stratum
Progression-Free Survival (Oxaliplatin)
时间窗: Overall study
Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression
次要结局
- Objective Tumor Response Rate (Oxaliplatin)(Overall study)
- Overall Survival (Irinotecan)(Overall study)
- Time to Treatment Failure (Irinotecan)(Overall Study)
- Overall Survival (Oxaliplatin)(Overall study)
- Objective Tumor Response Rate (Irinotecan)(Overall Study)
- Time to Progression (Oxaliplatin)(Overall Study)
- Time to Treatment Failure (Oxaliplatin)(Overall study)
- Progression-free Survival (Irinotecan)(Overall Study)
- Time to Progression (Irinotecan)(Overall Study)