Systemic Chemotherapy Plus HAI(FUDR）vs Systemic Chemotherapy Alone For CRCLM

Study Overview
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Brief Summary
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The aim of the trial is to optimize the overall survival of patients with resectable colorectal liver metastasis who have undergone liver metastasis resection. The patients will be treated with systemic chemotherapy plus hepatic arterial infusion With floxuridine, or with systemic chemotherapy only

Official Title
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Systemic Chemotherapy Plus HAI(FUDR）vs Systemic Chemotherapy Alone As Adjuvant Therapy in Patients With Resectable Colorectal Liver Metastasis

Conditions
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Colorectal Cancer, Liver Metastases, HAI

Intervention / Treatment
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* Drug: FUDR
* Drug: Oxaliplatin
* Drug: Leucovorin
* Drug: 5FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 years old Histologically confirmed colorectal adenocarcinoma Radiologically or pathologically confirmed diagnosis of colorectal liver metastasis besides systematic chemotherapy，with no prior treatment for liver metastasis, including operation, radiotherapy,HAI, transcatheter hepatic arterial chemoembolization (TACE) and ablation. Without extra-hepatic metastasis confirmed by CT, MRI or PET/CT (if necessary) scanning With adequate bone marrow function: platelets ≥ 90 x 109/L; white blood cells ≥ 3×109/L; absolute neutrophil count (ANC) ≥ 1.5 x 109/L Serum bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 5 x ULN Patient has no ascites and with adequate blood coagulation function, albumin ≥ 35 g/L Grade A level of Child-Push Liver Function Creatinine ≤ 1× ULN, or Calculated Creatinine Clearance >50ml/min （Cockcroft-Gault Equation） ECOG performance status of 0-2 Life expectancy ≥ 3 months Not appropriate for anti-EGFR or any other targeted therapy (with KRAS mutation or could not afford it) Patients have provided a signed Informed Consent Form With good compliance Exclusion Criteria: With any extra-hepatic metastasis and/or primary tumor recurrence Severe arterial embolism or ascites With hemorrhagic tendency or coagulation disorders Hypertensive crisis or hypertensive encephalopathy Severe and uncontrolled systemic complications such as infections or diabetes. Serious cardiovascular diseases such as cerebrovascular accident (within 6 months before enrollment), myocardial infarction (within 6 months before enrollment), uncontrolled hypertension even with appropriate drug intervention, unstable angina pectoris, congestive heart failure (NYHA 2-4 degree), arrhythmia that needs medication intervention Patient who has suffered from central nervous system diseases such as primary brain tumor, uncontrolled epilepsy even with standard treatment, any brain metastasis or stroke Patient who has a concurrent malignancy or has a malignancy within 5 years before study enrollment, (with the exception of radically resected skin basal cell carcinoma or cervical carcinoma in situ) Patient who has received any investigational antineoplastic agent within 28 days before the enrollment Any residual toxicity from prior chemotherapy (with the exception of alopecia), such as grade 2 or more sensory peripheral neuropathy (NCI CTC v3.0), oxaliplatin-based regimen will not be considered Patient who is allergic to oxaliplatin, leucovorin, 5-Fluorouracil, floxuridine or dexamethasone Pregnant or lactating women Patient who does not use or refuses to take any appropriate contraceptive measures (intrauterine contraceptive ring, barrier contraception combined with spermicidal gel or sterilization operation), including women of childbearing age (within 2 years after the last menstrual period) and men who are with possible fertility Unable or unwilling to comply with the research plan The existence of any other disease, dysfunction caused by metastatic lesions, or suspicious disease found on the regular examination, which indicating contraindications to the use of study drugs or may bring high risks of treatment related complications

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Systematic Chemotherapy + HAI(FUDR)<br>Patients will receive Systemic FOLFOX + HAI (FUDR) every 28 days: Oxaliplatin 85 mg/m2 ivd over 3 hours on Day 1,15; Leucovorin (l-LV) 200mg/m2 ivd over 2 hours on Day 1,15; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1,15. floxuridine (FUDR) 0.12mg/Kg/d,d1-14 and 25 mg dexamethasone in normal saline to a total volume of 300 ml will be administered through the HAI pump. This will be repeated on Day 1 of each 28-day cycle. FUDR will be administered through a 14-day continuous infusion with the HAI pump. | Drug: FUDR<br>* Floxuridine(FUDR) 0.12 mg/kg/day，on Day 1-14 through the HAI pump.<br>* Other names: Floxuridine;Drug: Oxaliplatin<br>* Oxaliplatin 180 mg/m2 IV over 90 minutes on Day 1, 15.<br>Drug: Leucovorin<br>* Leucovorin 200mg/m2 ivd over 2 hours on Day 1<br>Drug: 5FU<br>* followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.<br>* Other names: 5-Fluorouracil;|
| Active Comparator: Systematic Chemotherapy<br>Patients will receive FOLFOX every every 28 days: Oxaliplatin 85 mg/m2 ivd over 3 hours on Day 1,15; Leucovorin (l-LV) 200mg/m2 ivd over 2 hours on Day 1,15; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1,15. | Drug: Oxaliplatin<br>* Oxaliplatin 180 mg/m2 IV over 90 minutes on Day 1, 15.<br>Drug: Leucovorin<br>* Leucovorin 200mg/m2 ivd over 2 hours on Day 1<br>Drug: 5FU<br>* followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.<br>* Other names: 5-Fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3 Year Relapse Free Survival Rate | From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 monthes | up to 36 monthes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | From date of randomization until the date of death from any cause, assessed up to 4 years | up to 4 years |