NCT03164655已完成2 期
A Randomized Phase II Study Comparing Treatment Intensification With CIAH Plus Systemic Chemotherapy to Systemic Chemotherapy Alone in Patients With Liver-only Colorectal Metastases Considered Still Non Resectable After at Least Two Months of Systemic Induction Chemotherapy
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- UNICANCER
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM
研究概览
简要总结
National trial, multicenter, randomized, phase II comparing treatment intensification with hepatic arterial infusion chemotherapy plus systemic chemotherapy (CT) to systemic chemotherapy alone in patients with liver-only colorectal metastases (CRLM) considered still non resectable after at least two months of systemic induction chemotherapy.
详细描述
to compare the efficacy of CT intensification combining hepatic arterial infusion(HAI) oxaliplatin plus IV FOLFIRI plus targeted therapy (anti-epidermal growth factor receptor (EGFR) or bevacizumab) to conventional systemic CT alone plus targeted therapy (anti-EGFR or antiangiogenic antibody), in patients with liver-only CRLM not amenable to curative-intent resection (and/or ablation) after systemic induction CT in terms of conversion to complete (R0 R1) resection (or ablation) rate (CRR).
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
- Double (Participant, Investigator)
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
- •Histologically confirmed colorectal cancer (CRC), and radiologic or histologic proof of CRLM not amenable to a curative intent-treatment.
- •At least two months of prior induction systemic CT with oxaliplatin and/or irinotecan combined with a fluoropyrimidine combined or not to a targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) for metastatic disease (patients ending their adjuvant chemotherapy after primary tumor resection since more than 6 months should also have received first-line chemotherapy for metastatic disease). Further systemic chemotherapy lines are allowed.
- •Unresectability of the CRLM will be confirmed by a centralized multidisciplinary expert panel (composed of surgeons, radiologists, interventional radiologists and medical oncologists). The panel will review the CT scan and MRI of the patients (weekly web conference). Non-resectability criteria (one of the following criteria):
- •Upfront R0/R1 resection of all CRLM (that leaves at least two adequately perfused and drained segments) is not possible
- •and/or metastases in contact with major vessels of the remnant liver which would require resection of the vessel for an R0 resection (i.e., tumor involvement of main portal right and left portal veins, of the three main hepatic veins, or of the retrohepatic vena cava)
- •and/or documented progressive disease on imaging (according to the RECIST v1.1) or doubling of serum levels of carcinoembryonic antigen (CEA) or carbohydrate antigen 19-9 (CA 19-9) following ≥2 months of induction CT
- •At least one measurable liver metastasis according to the RECIST v1.1
- •Age ≥18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Normal liver function, i.e. bilirubin <1.5 times the upper limit of normal values (ULN), aminotransferases <5 ULN, alkaline phosphatase <5 ULN
- •International normalized ratio (INR) <1.5 ULN
- •Neutrophils >1500/mm³, platelets >100 000/mm³, hemoglobin >9 g/dL (transfusion allowed)
- •Calculated creatinine clearance >50 mL/min (Cockcroft and Gault formula)
- •Informed consent signed by the patient or his/her legal representative
- •Patient affiliated to a social security regimen
- •Potentially reproductive patients must agree to use an effective contraceptive method or practice adequate methods of birth control or practice complete abstinence while on treatment, and for at least 6 months after the last dose of study drug.
- •Uracilemia <16 ng/ml
排除标准
- •Patient eligible for curative-intent treatment of CRLM (i.e. resection and/or thermoablation), according to the local multidisciplinary team and/or the central review.
- •Definitive anatomical contraindication to complete surgical resection (any of the following criteria):
- •More than two lesions in all liver segments
- •Bilobar liver metastasis and more than three lesions >3 cm in the hepatic lobe the least affected (i.e. the future remnant liver)
- •Bilobar liver metastasis and disease liver extend >50%
- •Extrahepatic tumor disease (except ≤3 lung nodules <10 mm deemed amenable to curative-intent resection/thermoablation and non-resected primary tumor with no or mild symptoms)
- •Patient with contraindication for trial drugs (investigators have to refer to drugs SmPC); contraindication limited to targeted therapy (e.g., anti-EGFR or antiangiogenic antibody) is not an exclusion criteria
- •Disease progression after FOLFOXIRI/FOLFIRINOX
- •Sensory neuropathy ≥ grade 2 (National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0)
- •If patients received bevacizumab, following non-inclusion criteria must be respected:
- •Proteinuria >1 g,
- •Gastro-intestinal fistulae or perforation,
- •Hypersensitivity to Chinese hamster ovary cell products or other human recombinant antibody,
- •Major surgery in the last 28 days.
- •If patients received panitumumab, following non-inclusion criteria must be respected:
- •Interstitial lung disease,
- •Pulmonary fibrosis.
- •Significant chronic liver disease (resulting in portal hypertension and/or liver insufficiency)
- •Allergy to contrast media that cannot be managed with standard care
- •Previous organ transplantation, HIV or other immunodeficiency syndromes
- •Concomitant or past history of cancer within 5 years prior to entry into the trial other than adequately treated basal-cell skin cancer or in situ carcinoma of the cervix
- •Patients with clinically significant active heart disease or myocardial infarction in the last 6 months
- •Concomitant medications/comorbidities that may prevent the patient from receiving study treatments as uncontrolled intercurrent illness (for instance: active infection, active inflammatory disorders, inflammatory bowel disease, intestinal obstruction, uncontrolled hypertension systolic >15 and diastolic >9, symptomatic congestive heart failure...)
- •Ionic disorders as:
- •Kalemia ≥1 x ULN
- •Magnesemia <0.5 mmol/L
- •Calcemia <2 mmol/L
- •Patient with a dihydropyrimidine dehydrogenase (DPD) deficiency; Uracilemia ≥16 ng/ml, the test should be done for all patients before first 5-FU administration, according to "agence nationale de sécurité du médicament" (ANSM) communication regarding recommendation about high risk of no testing DPD in patient before 5-FU administration
- •QT/QTc >450 msec for men and > 470 msec for women
- •Concomitant intake of St. John's wort
- •Patient already included in another clinical trial with an experimental treatment
- •Pregnancy or lactation
- •Patients deprived of liberty or under guardianship
- •Patients unable to undergo medical monitoring test for geographical, social or psychological reasons
研究组 & 干预措施
HAI oxaliplatin combined with I.V. FOLFIRI + target therapy
Experimental
- HAI oxaliplatin 100 mg/m² on D1
- I.V. cetuximab 500 mg/m² or panitumumab 6 mg/kg or bevacizumab 5 mg/kg D1 according to RAS status and prior response/tolerance to systemic induction CT
- modified FOLFIRI regimen without fluorouracil bolus
- I.V. irinotecan 180 mg/m² D1
- I.V. bolus 5-Fluorouracil (5-FU): 0
- I.V. leucovorin 400 mg/m² in 2 hours D1
- I.V. continuous infusion 5-FU 2400 mg/m² in 46 hours
干预措施: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil (Drug)
conventional systemic CT
Active Comparator
- Response to systemic induction CT
- Toxicity and duration of the systemic induction CT
- RAS status
- Current guidelines/standard of care
干预措施: Oxaliplatin, Cetuximab, Bevacizumab, Panitumumab, Irinotecan, Leucovorin, 5-Fluorouracil (Drug)
结局指标
主要结局
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM
时间窗: 6 months
Curative-intent (R0-R1) resection (and/or ablation) rate (CRR) of CRLM confirmed by a systematic review of the surgical and pathological report by an independent committee blind to the treatment received
次要结局
未报告次要终点
研究者
研究点 (4)
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