mFOLFOXIRI Compared to mFOLFOX6 or CapeOx as Adjuvant Chemotherapy for Stage IIIB or IIIC Colorectal Cancer

mFOLFOXIRI Compared to mFOLFOX6 or CapeOx as Adjuvant Chemotherapy for Stage IIIB or Stage IIIC Colorectal Cancer: A Randomized Controlled Clinical Research

This study will focus on postoperative patients of stage IIIB or stage IIIC colorectal cancer. These patients will start to accept chemotherapy in 3-4 weeks after operation, these patients were randomly divided into two groups, one group will accept adjuvant chemotherapy of mFOLFOX6 or CapeOX; another group will use mFOLFOXIRI, they can change the regimen to mFOLFOX6 or CapeOx after accepting not less than two complete chemotherapy regimen, if can not tolerate the adverse reaction of mFOLFOXIRI. The efficacy and safety of adjuvant chemotherapy will be compared between the two groups. Disease-free survival, overall survival, incidence of adverse reaction of chemotherapy and postoperative quality of life will be recorded.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: mFOLFOXIRI; Drug: mFOLFOX6 OR CapeOx

Detailed Description

This trial is a two-arm, open labelled, prospective, randomized phase II studies. The postoperative stage of eligible patients was stage IIIB or stage IIIC. These high risk patients will be randomly assigned, in a 1:1 ratio, to receive either mFOLFOXIRI or mFOLFOX6/CapeOx for 6 months as adjuvant chemotherapy.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ye Lechi, M.D.; Phone Number: 008613868803676; Email: yljwenzhou@126.com

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Ye Lechi, M.D.; Phone Number: 008613868803676; Email: yljwenzhou@126.com

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:

• Age 18-75 years
• ECOG PS 0-1
• Curative surgery (R0 resection)
• ypStage III B and ypStage III C
• No distant metastasis after surgery

Exclusion Criteria:

• any treatment before surgery including chemotherapy, radiotherapy and targeted agents.
• Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
• Heart failure grade III/IV (NYHA-classification).
• Unresolved toxicity higher than CTCAE v.4.0 Grade 1 attributed to any prior therapy/procedure.
• Subjects with known allergy to the study drugs or to any of its excipients.
• Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
• Breast- feeding or pregnant women
• Lack of effective contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: mFOLFOXIRI adjuvant chemotherapy; Patients will receive mFOLFOXIRI once every two weeks for 12 cycles as adjuvant chemotherapy. They can change the regimen to mFOLFOX6 or CapeOx after accepting not less than two complete chemotherapy regimen, if can not tolerate the adverse reaction of mFOLFOXIRI. Total 24 weeks.	Drug: mFOLFOXIRI; mFOLFOXIRI (oxaliplatin 85 mg/m2, irinotecan 150-165 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400-2800mg/m2 as a 46-48 hour continuous infusion on day 1); Other Names: Leucovorin; Irinotecan; 5-Fluorouracil; Oxaliplatin; Drug: mFOLFOX6 OR CapeOx; mFOLFOX6(oxaliplatin 85 mg/m2, folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-48 hour continuous infusion on day 1) CapeOx(Oxaliplatin 130 mg/m2 intravenous infusion on day 1,Capecitabine 1000 mg/m2 twice daily PO for 14 days); Other Names: Capecitabine; Leucovorin; 5-Fluorouracil; Oxaliplatin
ACTIVE_COMPARATOR: mFOLFOX6 or CapeOx adjuvant chemotherapy; Patients will receive mFOLFOX6 once every two weeks for 12 cycles as adjuvant chemotherapy or CapeOx once every three weeks for 8 cycles as adjuvant chemotherapy. Total 24 weeks.	Drug: mFOLFOX6 OR CapeOx; mFOLFOX6(oxaliplatin 85 mg/m2, folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-48 hour continuous infusion on day 1) CapeOx(Oxaliplatin 130 mg/m2 intravenous infusion on day 1,Capecitabine 1000 mg/m2 twice daily PO for 14 days); Other Names: Capecitabine; Leucovorin; 5-Fluorouracil; Oxaliplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Disease-free survival	Defined as the time from randomization to relapse or death, whichever occurred first	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 5.0.	Safety	up to 3 years
Overall survival	Defined as the time from randomization to death from any cause	up to 3 years
QLQ-C30 Quality of Life questionnaire	postoperative quality of life	up to 3 years
Quality of Life assessed by SF-36	postoperative quality of life	up to 3 years

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Wenzhou Medical University

Publications and helpful links

General Publications

• Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crino L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. doi: 10.1200/JCO.2006.09.0928.
• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
• Stintzing S. Management of colorectal cancer. F1000Prime Rep. 2014 Nov 4;6:108. doi: 10.12703/P6-108. eCollection 2014.
• Walker R, Wood T, LeSouder E, Cleghorn M, Maganti M, MacNeill A, Quereshy FA. Comparison of two novel staging systems with the TNM system in predicting stage III colon cancer survival. J Surg Oncol. 2018 Apr;117(5):1049-1057. doi: 10.1002/jso.25009. Epub 2018 Feb 23.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 1, 2022
• Primary Completion (ANTICIPATED): June 30, 2024
• Study Completion (ANTICIPATED): June 30, 2025

Study Registration Dates

• First Submitted: January 18, 2022
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (ACTUAL): January 20, 2022

Study Record Updates

• Last Update Posted (ACTUAL): January 20, 2022
• Last Update Submitted That Met QC Criteria: January 18, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Colorectal Cancer; FOLFOXIRI; Stage IIIB; Stage IIIC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Capecitabine; Oxaliplatin; Leucovorin; Irinotecan; Levoleucovorin
• Other Study ID Numbers: T-idea

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No