NCT03635021进行中（未招募）3 期
Phase III Randomized Sequential Open-label Study to Evaluate the Efficacy of FOLFOX + Panitumumab Followed by FOLFIRI + Bevacizumab (Sequence 1) Versus FOLFOX + Bevacizumab Followed by FOLFIRI + Panitumumab (Sequence 2) in Untreated Patients With Wild-type RAS Metastatic, Primary Left-sided, Unresectable Colorectal Cancer: The CR-SEQUENCE
Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)1 个研究点 分布在 1 个国家目标入组 419 人开始时间: 2018年10月15日最近更新:
适应症
干预措施
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 419
- 试验地点
- 1
- 主要终点
- Progression-free survival rate at 35 months
研究概览
简要总结
The purpose of this study is to assess the efficacy of FOLFOX + panitumumab followed by FOLFIRI + bevacizumab (Sequence 1) versus FOLFOX + bevacizumab followed by FOLFIRI + panitumumab (Sequence 2) in untreated patients with wild-type RAS metastatic, primary left-sided, unresectable 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
- •Man or woman at least 18 years old.
- •Capable of understand, sign and date an informed consent approved by an IEC.
- •Histologically confirmed adenocarcinoma of the left colon or rectum (originate in the splenic flexure, descending colon, sigmoid colon, or rectum) in patients with unresectable (not amenable to radical surgery of metastases at the study inclusion) metastatic (M1) disease.
- •Patients who had wild-type RAS status confirmed as per standard of care according to international guidelines prior to first-line initiation.
- •*RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117)
- •At least one unidimensionally measurable lesion per RECIST criteria (version 1.1).
- •ECOG performance status <
- •Adequate bone marrow function: neutrophils ≥1.5 x109 / L; platelets ≥100 x109 /L; haemoglobin ≥ 9 g/dL.
- •Hepatic, renal and metabolic function as follows:
- •Total bilirubin count ≤1.5 x upper limit of normal (ULN), serum glutamic pyruvic transaminase/alanine aminotransferase (SGPT/ALT) and serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST) ≤ 2.5 x ULN (5 x ULN for subjects with liver involvement of their cancer or 10 x ULN for subjects with bone involvement).
- •Renal function, calculated as creatinine clearance or 24-hour creatinine clearance ≥ 50 mL/min.
排除标准
- •History of prior or concurrent central nervous system metastases.
- •History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for ≥ 5 years before randomization.
- •Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma.
- •Prior adjuvant chemotherapy for colorectal cancer (stage I, II or III) terminated less than 6 month before metastatic disease was diagnosed.
- •Unresolved toxicities of a previous systemic treatment that, in the opinion of the Investigator, cause the patient unfit for inclusion.
- •Prior use (as monotherapy or adjuvant treatment) of anti-EGFR antibody therapy (e.g. cetuximab), anti-VEGF or small molecule EGFR inhibitors (e.g. erlotinib).
- •Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins ≤ 30 days before inclusion.
- •Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia.
- •Uncontrolled hypertension.
- •History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography (CT).
- •Treatment for systemic infection within 14 days before the start of study treatment.
- •Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade ≥ 2 diarrhoea according to NCI-CTCAE version 4.03).
- •Clinically significant peripheral sensory neuropathy.
- •Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment.
- •History of Gilbert disease or known dihydropyrimidine deficiency syndrome.
- •Recent (within 6 months before the start of study treatment) gastroduodenal ulcer to be active or uncontrolled.
- •Recent (within 6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or other significant venous event.
- •Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy (within 6 months before the start of study treatment)
- •Recent (within 4 weeks prior to inclusion in the study) major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery
- •History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results.
- •Known positive test for human immunodeficiency virus infection, hepatitis C virus, and chronic active hepatitis B infection.
- •Any disorder that compromises the patient's ability to provide written informed consent and/or comply with study procedures.
- •Any investigational agent within 30 days prior to inclusion.
- •Pregnant or breastfeeding woman.
- •Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study.
- •Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g. diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men.
- •The patient is unwilling or unable to meet the requirements of the study.
- •Psychological, geographical, familial or sociological conditions that potentially prevent compliance with the study protocol and follow-up schedule.
研究组 & 干预措施
Sequence 1
Experimental
FOLFOX regimen panitumumab FOLFIRI regimen bevacizumab
干预措施: FOLFOX regimen (Drug)
Sequence 1
Experimental
FOLFOX regimen panitumumab FOLFIRI regimen bevacizumab
干预措施: Panitumumab (Drug)
Sequence 1
Experimental
FOLFOX regimen panitumumab FOLFIRI regimen bevacizumab
干预措施: Bevacizumab (Drug)
Sequence 1
Experimental
FOLFOX regimen panitumumab FOLFIRI regimen bevacizumab
干预措施: FOLFIRI regimen (Drug)
Sequence 2
Experimental
FOLFOX regimen bevacizumab FOLFIRI regimen panitumumab
干预措施: FOLFOX regimen (Drug)
Sequence 2
Experimental
FOLFOX regimen bevacizumab FOLFIRI regimen panitumumab
干预措施: Panitumumab (Drug)
Sequence 2
Experimental
FOLFOX regimen bevacizumab FOLFIRI regimen panitumumab
干预措施: Bevacizumab (Drug)
Sequence 2
Experimental
FOLFOX regimen bevacizumab FOLFIRI regimen panitumumab
干预措施: FOLFIRI regimen (Drug)
结局指标
主要结局
Progression-free survival rate at 35 months
时间窗: 35 months after date of randomization
35-month PFSR defined as the number of patients, who at 35 months after randomization, have not had second or first disease progression nor died (due to any cause), over the total number of evaluable patients.
次要结局
- time to first-line treatment failure and to second-line treatment failure(72 months)
- Depth of Response(Baseline through the end of the study (up 72 months))
- overall survival rate at 35 months(35 months after date of randomization)
- progression-free from randomization to second progression or death(Baseline through the end of the study (up 72 months))
- progression-free survival in first-line treatment and in second-line treatment(Baseline through the end of the study (up 72 months))
- objective response rate(Baseline through the end of the study (up 72 months))
- duration of disease control(Baseline through the end of the study (up 72 months))
- Incidence and severity of AEs CTCAE v4.03 criteria(Baseline through the end of the study (up 72 months))
- overall survival(Baseline through the end of the study (up 72 months))
- proportion of patients with Early Tumour Shrinkage(Baseline through the end of the study (up 72 months))
- disease control rate(Baseline through the end of the study (up 72 months))
- duration of response(Baseline through the end of the study (up 72 months))
- time to response(Baseline through the end of the study (up 72 months))
研究者
研究点 (1)
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