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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Metastasis
• Intervention / Treatment: Drug: FUDR +oxaliplatin; Drug: oxaliplatin+Leucovorin+5-FU

• Study Type: Interventional
• Enrollment (Anticipated): 700
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianmin Xu, MD; Phone Number: 86-13764476150; Email: xujmin@aliyun.com

Study Locations

• China
  • Shanghai, China, 200032
    • Recruiting
    • Zhongshan Hospital, Fudan University
    • Contact: Wenju Chang, MD; Phone Number: 86-21-13764476150
    • Principal Investigator: jianmin xu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IPC plus AC; 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; IPC: one dose of fluorodeoxyuridine (FUDR) 1000 mg and oxaliplatin 100 mg were administered as a bolus into the regional vein; Other Names: fluorodeoxyuridine (FUDR); Drug: oxaliplatin+Leucovorin+5-FU; Adjuvant chemotherapy (AC): All patients received mFOLFOX6 adjuvant chemotherapy: oxaliplatin+Leucovorin+5-FU; Other Names: Leucovorin (LV)
Active Comparator: AC; 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; Adjuvant chemotherapy (AC): All patients received mFOLFOX6 adjuvant chemotherapy: oxaliplatin+Leucovorin+5-FU; Other Names: Leucovorin (LV)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Xu jianmin
• Collaborators: Ruijin Hospital; Zhejiang University; The Second Affiliated Hospital of Harbin Medical University
• Investigators: Study Director: Hong Jiang, MD, Fudan University

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Anticipated): February 1, 2020
• Study Completion (Anticipated): February 1, 2022

Study Registration Dates

• First Submitted: March 20, 2015
• First Submitted That Met QC Criteria: March 25, 2015
• First Posted (Estimate): March 31, 2015

Study Record Updates

• Last Update Posted (Estimate): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 25, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: prevention; adjuvant chemotherapy; intraportal chemotherapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antidotes; Vitamin B Complex; Oxaliplatin; Leucovorin; Levoleucovorin; Floxuridine
• Other Study ID Numbers: IICCAC; 82345432 (Other Grant/Funding Number: Shanghai key research projects)