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

Phase 3

• Conditions: Metastasis; Colorectal Cancer
• Interventions: Drug: FUDR +oxaliplatin; Drug: oxaliplatin+Leucovorin+5-FU

• Registration Number: NCT02402972
• Lead Sponsor: Xu jianmin

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2015-01
• Study Start: 2015-02
• Study First Submitted: 2015-03-20
• Study First Submitted QC: 2015-03-25
• Last Update Submitted: 2015-03-25
• Study First Posted: 2015-03-31
• Last Update Posted: 2015-03-31
• Primary Completion: 2020-02
• Study Completion: 2022-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 700

Inclusion Criteria

1. Age ≥ 18 and ≤ 75 years;
2. 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).
3. 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)
4. Performance status (ECOG) 0~1
5. Adequate hematological function: Neutrophils≥1.5 x109/l and platelet count≥100 x109/l; Hb ≥9g/dl (within 1 week prior to randomization)
6. 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);
7. Written informed consent for participation in the trial.

Exclusion Criteria

1. Previous exposure to prior cancer therapy (chemotherapy, radiotherapy or intervention therapy) for colon cancer.
2. Patients with known hypersensitivity reactions to any of the components of the study treatments.
3. 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
4. Pregnancy (absence confirmed by serum/urine β-HCG) or breast-feeding
5. Known drug abuse/ alcohol abuse
6. Legal incapacity or limited legal capacity
7. Pre-existing peripheral neuropathy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IPC plus AC	oxaliplatin+Leucovorin+5-FU	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.
IPC plus AC	FUDR +oxaliplatin	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.
AC	oxaliplatin+Leucovorin+5-FU	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.

Primary Outcome Measures

Name	Time	Method
disease-free survival	up to 5 year	DFS was defined as from the date of randomization to the date of tumor recurrence or death from any cause.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, China