NALIRIFOX Plus Targeted Therapy Versus FOLFOX Plus Targeted Therapy as First-line Treatment for Metastatic Colorectal Cancer

NALIRIFOX Plus Targeted Therapy Versus FOLFOX Plus Targeted Therapy as First-line Treatment for Metastatic Colorectal Cancer: a Multicentre, Open-label, Randomised Trial

To explore the safety and efficacy of NALIRIFOX plus targeted therapy versus FOLFOX plus targeted therapy as first-line treatment for metastatic colorectal cancer.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer (CRC)
• Intervention / Treatment: Drug: NALIRIFOX plus targeted therapy; Drug: FOLFOX plus targeted therapy

Detailed Description

This is a multicentre, open-label, randomised study to explore the safety and efficacy of NALIRIFOX plus targeted therapy versus FOLFOX plus targeted therapy as first-line treatment for metastatic colorectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 144
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Tianshu Liu, Doctor; Phone Number: +86-21-64041990; Email: liu.tianshu@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai Zhongshan Hospital
    • Contact: Phone Number: +86-21-64041990

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥18 years old
• Histopathologically confirmed patient with an inoperable metastatic colorectal adenocarcinoma
• The unresectable stage of metastatic disease has not received any systemic antitumor therapy
• For subjects previously receiving neoadjuvant or adjuvant therapy, the date of first discovery of disease progression must be at least 12 months removed from the date of last administration of neoadjuvant or adjuvant therapy
• The presence of at least 1 measurable lesion that can be evaluated according to the RECIST v1.1 criteria
• ECOG 0~1
• Normal bone marrow and organ function
• Understand the situation of this study, patients and/or legal representatives voluntarily agree to participate in this study and sign informed consent form

Exclusion Criteria:

• Patients with known MSI-H or dMMR who were evaluated by investigators as suitable for treatment with immune checkpoint inhibitors.
• Patients allergic to the investigational drug and its excipients
• Underweight (body mass index [BMI]<18.5 kg/m^2
• Known or suspected central nervous system metastasis
• Received irinotecan before enrollment
• Had undergone surgery and other oncologic treatments within the first 4 weeks of enrollment
• Previous treatment-related toxicity didn't return to NCI-CTCAE v5.0 class I or below.
• The use of CYP3A, CYP2C8, and UGT1A1 inhibitors or inducers couldn't be discontinued or were not discontinued within 2 weeks prior to enrollment
• Serious gastrointestinal disorders
• Interstitial lung disease
• Tendency of arterial embolism and massive bleeding within 6 months before enrollment (except surgical bleeding)
• Patients with fluid accumulation that couldn't reach a stable state and small amount of pleural effusion or ascites on imaging without clinical symptoms could be enrolled
• Intestinal obstruction, or a risk of intestinal obstruction in the short term
• Gastrointestinal perforation, intraperitoneal abscess, and fistula
• Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, heart disease, active bleeding, active viral infection, etc
• Have had other malignancies within the past 5 years or currently, except cured cervical carcinoma in situ, uterine carcinoma in situ, and non-melanoma skin cancer
• Patients of childbearing age who refuse to take contraceptives, women who are pregnant or breastfeeding
• The researchers didn't consider it appropriate to participate in this study

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: NALIRIFOX plus targeted therapy	Drug: NALIRIFOX plus targeted therapy; Drug: Irinotecan Liposome Irinotecan liposome injection will be administered by an intravenous infusion at the dose of 50 mg/m^2, d1, 14 days per cycle. Drug: Oxaliplatin 75 mg/m^2, intravenously infusion, d1, 14 days per cycle. Drug: 5-FU 2400mg/m^2, intravenous infusion, d1-2, 14 days per cycle. Drug: LV/l-LV 400mg/m^2 or 200mg/m^2 , intravenous infusion, d1, 14 days per cycle. Drug: Bevacizumab 5mg/kg, intravenous infusion, d1, 14 days per cycle. Drug: Cetuximab 500mg/m^2, intravenous infusion, d1, 14 days per cycle.
Active Comparator: FOLFOX plus targeted therapy	Drug: FOLFOX plus targeted therapy; Drug: Oxaliplatin 85 mg/m^2, intravenously infusion, d1, 14 days per cycle. Drug: 5-FU 2400mg/m^2, intravenous infusion, d1-2, 14 days per cycle. Drug: LV/l-LV 400mg/m^2 or 200mg/m^2 , intravenous infusion, d1, 14 days per cycle. Drug: Bevacizumab 5mg/kg, intravenous infusion, d1, 14 days per cycle. Drug: Cetuximab 500mg/m^2, intravenous infusion, d1, 14 days per cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
18 month PFS rate	To investigate the preliminary antitumor efficacy of study.	Eighteen months after the randomization of research participants

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	To investigate the preliminary antitumor efficacy of study.	From date of randomization until the date of first documented progression、termination of treatment, or date of death from any cause, whichever came first, assessed up to 12 months
Disease control rate	To investigate the preliminary antitumor efficacy of study.	From date of randomization until the date of first documented progression、termination of treatment, or date of death from any cause, whichever came first, assessed up to 12 months
Progression free survival	To investigate the preliminary antitumor efficacy of study.	From date of randomization until the date of first documented progression、termination of treatment, or date of death from any cause, whichever came first, assessed up to 12months
R0 resection	To assess surgical conversion rates in patients who could be surgically resected.	From date of randomization until the date of surgical resection, assessed up to 12 months
Overall survival	To investigate the preliminary antitumor efficacy of study.	From date of randomization until the date of death from any cause, assessed up to 30 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2025
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: December 28, 2025
• First Posted (Actual): December 30, 2025

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 28, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Folfox protocol
• Other Study ID Numbers: CSPC-DEY-CRC-K10

Drug and device information, study documents

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