A Multi-center Randomized Controlled Trial of Intraportal Chemotherapy Combined With Adjuvant Chemotherapy (mFOLFOX6) for Stage II and III Colon Cancer

Study Overview
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Brief Summary
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To investigate whether intraoperative intraportal chemotherapy combined with adjuvant chemotherapy as treatment could improve disease-free survival (DFS) in patients with curative colorectal cancer resection compared with adjuvant chemotherapy alone. This is a prospective, blind (doctors who done outcome measures were masked), multi-center, 2-arm randomized controlled trial.

Official Title
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A Multi-center Randomized Controlled Trial: Intraportal Chemotherapy Combined With Adjuvant Chemotherapy (mFOLFOX6) for Stage II and III Colon Cancer

Conditions
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Colorectal Cancer, Metastasis

Intervention / Treatment
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* Drug: FUDR +oxaliplatin
* Drug: oxaliplatin+Leucovorin+5-FU


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 and ≤ 75 years; Primary tumor has undergone histologically confirmed colon adenocarcinoma; Colon cancer was defined by the presence of the inferior pole of the tumor above the peritoneal reflection (at least 15 cm from the anal margin). Together with clinical or radiological evidence of Stage II (T3-4, N0, M0) or Stage III (T1-4, N1-2, M0) disease (according to the 2007 revision of the International Union Against Cancer TNM staging system) Performance status (ECOG) 0 1 Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization) Adequate hepatic and renal function: Serum bilirubin≤1.5 x upper limit of normal (ULN), alkaline phosphatase ≤5x ULN, and serum transaminase (either AST or ALT) ≤ 5 x ULN(within 1 week prior to randomization); Written informed consent for participation in the trial. Exclusion Criteria: Previous exposure to prior cancer therapy (chemotherapy, radiotherapy or intervention therapy) for colon cancer. Patients with known hypersensitivity reactions to any of the components of the study treatments. Other previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding Known drug abuse/ alcohol abuse Legal incapacity or limited legal capacity Pre-existing peripheral neuropathy.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPC plus AC<br>patients treated with intraoperative intraportal chemotherapy (IPC) plus adjuvant chemotherapy (AC; mFOLFOX6).; IPC: During the operation, one dose of fluorodeoxyuridine (FUDR) 1000 mg and oxaliplatin 100 mg were administered as a bolus into the regional vein within 5 minutes just before ligation. AC: All patients received mFOLFOX6 adjuvant chemotherapy, consisting of a 2-h infusion of 85 mg/m2 oxaliplatin given simultaneously with a 2-h infusion of 400 mg/m2 LV, followed by a bolus of 400 mg/m2 5-FU, and then a continuous infusion of 2000 mg/m2 5-FU given on 2 consecutive days by intravenous pumping every 14 days for 12 cycles.[1] Adverse events were categorized according to National Cancer Institute Common Toxicity Criteria, version 3.0. | Drug: FUDR +oxaliplatin<br>* IPC: one dose of fluorodeoxyuridine (FUDR) 1000 mg and oxaliplatin 100 mg were administered as a bolus into the regional vein<br>* Other names: fluorodeoxyuridine (FUDR);Drug: oxaliplatin+Leucovorin+5-FU<br>* Adjuvant chemotherapy (AC): All patients received mFOLFOX6 adjuvant chemotherapy: oxaliplatin+Leucovorin+5-FU<br>* Other names: Leucovorin (LV);|
| Active Comparator: AC<br>patients treated with adjuvant chemotherapy (AC; mFOLFOX6) alone after surgery; Adjuvant chemotherapy (AC): All patients received mFOLFOX6 adjuvant chemotherapy, consisting of a 2-h infusion of 85 mg/m2 oxaliplatin given simultaneously with a 2-h infusion of 400 mg/m2 LV, followed by a bolus of 400 mg/m2 5-FU, and then a continuous infusion of 2000 mg/m2 5-FU given on 2 consecutive days by intravenous pumping every 14 days for 12 cycles.[1] Adverse events were categorized according to National Cancer Institute Common Toxicity Criteria, version 3.0. | Drug: oxaliplatin+Leucovorin+5-FU<br>* Adjuvant chemotherapy (AC): All patients received mFOLFOX6 adjuvant chemotherapy: oxaliplatin+Leucovorin+5-FU<br>* Other names: Leucovorin (LV);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival | DFS was defined as from the date of randomization to the date of tumor recurrence or death from any cause. | up to 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | OS was measured from the date of randomization to the date of death from any cause. | 3 year and 5 year | 
| metastasis-free survival | MFS was defined as the time from randomization to metastasis if metastasis was the first event. | 3 year and 5 year | 
| adverse events of Chemotherapy and IPC | toxicity (using NCI CTC 3.0) compared with mFOLFOX6 alone. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adjuvant chemotherapy, intraportal chemotherapy, prevention