Compare Efficacy and Safety of Raltitrexed-based and 5fu-based Neoadjuvant Chemotherapy for Colorectal Liver Metastasis

The Second Affiliated Hospital of Zhejiang University

This study is a multicenter ,randomization, open control study to evaluate the efficacy and safety of Raltitrexed-based chemotherapy and 5-fluorouracil-based chemotherapy in the peri-operative treatment of patients with Liver Metastasis From colorectal cancer (CRC).

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer; Liver Metastasis
• Intervention / Treatment: Drug: Raltitrexed-based chemotherapy; Drug: Raltitrexed-based chemotherapy; Drug: 5-fluorouracil-based chemotherapy; Drug: 5-fluorouracil-based chemotherapy

Detailed Description

The contrast analysis is separately done on Raltitrexed plus oxaliplatin and 5-fluorouracil plus oxaliplatin;Raltitrexed plus irinotecan and 5-fluorouracil plus irinotecan.To investigate the objective response rate,the R0 resection rate, the early tumor shrinkage （ETS）and depth of response(DPR) and the safety profile.

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • The Affiliated Tumor Hospital of Zhongshan University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital affiliated to Wuhan University
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Changhai Hospital of Shanghai
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of College of Medicine Zhejiang University
    • Hangzhou, Zhejiang, China, 310009
      • Second Affiliated Hospitalof Zhejiang University School of Medicine
    • Jinhua, Zhejiang, China, 321000
      • Jinhua People's Hospital
    • Ningbo, Zhejiang, China, 315010
      • The second hospital of Ningbo City

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. Histologically confirmed chinese colorectal cancer patients and imaging detection confirmed liver metastasis
2. previously no treatment for liver metastasis or Primary tumor had been removed and last additional chemotherapy over one year
3. Age of≥18 and ≤75
4. Adequate organ functions, as determined by normal bone marrow function (absolute neutrophil count2 x 109/L, platelets 100 x 109/L, White blood cells 4 x 109/L), liver function (serum bilirubin ≤ 2.5 x ULN, serum transaminases ≤2. 5x ULN)
5. ECOG≤1
6. Life Expectancy>6months
7. Signed written informed consent
8. Expected adequacy of follow-up

Exclusion Criteria:

1. Lesion is too small to assess by imaging
2. Extrahepatic metastases
3. Any anticancer chemotherapy in development within 4 weeks prior to study entry
4. Concurrent uncontrolled illness such as infection
5. Be allergic to medicines in the study
6. Pregnant or nursing patients
7. Fertile women (< 2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
8. Not willing or incapable to comply with all study visits and assessments
9. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that puts the patient at high risk for treatment-related complications.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltitrexed-based chemotherapy; Raltitrexed plus Oxaliplatin/Raltitrexed plus Irinotecan	Drug: Raltitrexed-based chemotherapy; Raltitrexed: 2.0mg,iv,15min,d1,Oxaliplatin:85mg/m2 iv,d1, q2w; Other Names: RTXOX; Drug: Raltitrexed-based chemotherapy; Raltitrexed: 2.0mg,iv,15min,d1,Irinotecan:180mg/m2 iv,d1, q2w; Other Names: RTXIRI
Active Comparator: 5-fluorouracil-based chemotherapy; 5-fluorouracil plus Oxaliplatin/5-fluorouracil plus Irinotecan	Drug: 5-fluorouracil-based chemotherapy; 5-fluorouracil:400mg/m2,ivp,2h,d1,1200mg/m2/d*2d(2400mg/m2,iv46-48h); Oxaliplatin:85mg/m2 iv,d1,q2w; Other Names: mFOLFOX6; Drug: 5-fluorouracil-based chemotherapy; 5-fluorouracil: 400mg/m2,ivp,2h,d1,1200mg/m2/d*2d(2400mg/m2,iv46-48h); Irinotecan:180mg/m2 d1, iv,q2w; Other Names: FOLFIRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate	38 months

Secondary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate of liver	38 months

Other Outcome Measures

Outcome Measure	Time Frame
The side effects of the treatment	38 months
The early tumor shrinkage （ETS）and depth of response(DPR)	38 months

Collaborators and Investigators

• Sponsor: Zhejiang University
• Investigators: Study Chair: Ding Ke-Feng, PHD/MD, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2015
• Primary Completion (Actual): September 11, 2018
• Study Completion (Actual): September 11, 2019

Study Registration Dates

• First Submitted: May 17, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimate): May 25, 2015

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 11, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: neoadjuvant chemotherapy; liver metastasis; Colorectal Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Folic Acid Antagonists; Fluorouracil; Raltitrexed
• Other Study ID Numbers: CRCLM-01