Randomized, Multicenter Phase II Study of Monoclonal FOLFOX6m + mAb Alone or in Combination With Liver Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease Limited to the Liver With Poor Prognosis
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 48
- 试验地点
- 8
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
Non-commercial, prospective, randomized, multicenter, national, phase II, open-label comparative clinical trial.
The patients will be randomized in a 1: 1 ratio in two arms:
Control arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab Experimental arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.
The main objective is to evaluate the radiological objective response rate according to the RECIST version 1.1 criteria at 6 months. Secondary objectives include: Evaluate overall survival, progression-free survival (PFS), safety profile, hepatic PFS, R0 liver surgery rate.
详细描述
Hepatic intra-arterial therapy (TACE) with irinotecan has been used in several prospective studies demonstrating an acceptable toxicity profile. Two randomized phase II studies have evaluated the efficacy of TACE with irinotecan compared to conventional chemotherapy in metastatic colon cancer. A second-line treatment study demonstrated an increase in PFS in the TACE versus FOLFIRI treatment arm.
A prospective open, randomized, multicenter phase II study is proposed that will include patients with liver metastases of colorectal origin with poor prognostic criteria.
LIFEPEARLS® is a CE marked medical device consisting of microspheres for use in chemoembolization. The device uses 100 +/- 50 micron microspheres of hydrogel into which chemotherapeutic agents are loaded and delivered into the hepatic artery to treat liver tumors. This device allows the continuous release of irinotecan in liver tumors causing a specific necrosis. The penetration of irinotecan into the tumor tissue is deeper thanks to the microspheres, avoiding proximal occlusion of the vessels supplying the tumor.
Systemic treatment will be administered according to the usual guidelines:
-FOLFOX6m for 6 months + monoclonal Ab (cycles are repeated every 15 days) Premedication: Dexamethasone 20 mg IV + ondansetron 8mg IV
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
- •Patients aged ≥ 18 years.
- •Patients with colorectal cancer and exclusive liver metastases with poor prognostic criteria,> 3 lesions and / or size> 5 cm. Patients with a diagnosis of liver metastases with synchronous presentation or with a disease-free interval may be included. If the primary tumor has not been resected, it must be clinically stable.
- •Measurable disease following RECIST version 1.1 criteria
- •Adequate bone marrow function, according to:
- •Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl can be transfused before inclusion in the study
- •Platelet count ≥ 100 x 109 / L
- •Absolute Neutrophil Count (ANC) ≥ 1.5x 109 / L
- •Adequate liver function, according to:
- •Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
- •Alkaline phosphatase ≤ 5 x ULN or ≤10 x ULN in the presence of bone metastases
- •Adequate renal function, with creatinine levels <1.5 mg / dL. Blood Ureic Nitrogen (BUN)> 50 ml / min.
- •Albumin> 3.0 g / dL
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-
- •Patients capable of understanding the information and giving their written informed consent to participate in the study
- •Women of childbearing potential must commit to sexual abstinence or use of barrier contraceptive methods during the study and must have a negative pregnancy test.
排除标准
- •Extension of the disease> 50% of the liver parenchyma (evaluated by CT performed within the month prior to inclusion)
- •Previous chemotherapy treatment for metastatic colorectal cancer
- •Clinically significant cardiovascular diseases: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure of New York Heart Association (NYHA) grade II or higher or severe cardiac arrhythmia.
- •History of malignancy in the last three years, except for basal cell carcinoma of the skin or carcinoma in situ of the cervix treated appropriately.
- •Altered coagulation (Quick> 50%)
- •Patients with active infectious processes
- •Patients with any of the contraindications specified in the technical data sheet of the study drug or with allergies to some of the drugs used
- •Pregnant or lactating patients
- •Portal thrombosis
- •Severe portal hypertension
- •Extrahepatic metastases
研究组 & 干预措施
Experimental
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab) + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.
干预措施: FOLFOX regimen (Drug)
Control
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab).
干预措施: FOLFOX regimen (Drug)
Experimental
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab) + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.
干预措施: LIVERPEARLS-Irinotecan (Drug)
Control
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab).
干预措施: Anti-EGFR or Bevacizumab (Biological)
Experimental
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab) + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.
干预措施: Anti-EGFR or Bevacizumab (Biological)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Evaluated at 6 months after first investigation drug administration.
The proportion of patients with tumor size reduction according to RECIST 1.1 criteria at 6 months
次要结局
- Progression free survival(Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks)
- Frequency of adverse events(Through study completion, average 2 years)
- Proportion of patients with liver surgery(Through study completion, average 2 years.)
- Overall Survival (OS)(Through study completion, average 2 years)
- Hepatic Progression free survival(Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks)