FULIRI Plus Targeted Therapy for First-line Conversion Therapy of Colorectal Cancer Liver Metastases.

A Phase II Clinical Study of FULIRI Regimen Chemotherapy Combined With Targeted Therapy for First-line Conversion Treatment of Colorectal Cancer Liver Metastases.

This study is a single-center, prospective, randomized, single-arm phase II clinical trial designed to evaluate the safety and efficacy of FULIRI chemotherapy regimen combined with targeted therapy (bevacizumab/cetuximab) as first-line conversion therapy for colorectal cancer with liver metastases. Eligible patients with colorectal cancer and liver metastases, after signing informed consent, received FULIRI chemotherapy combined with bevacizumab/cetuximab targeted therapy. Efficacy was assessed after every four treatment cycles, followed by multidisciplinary team (MDT) discussion regarding potential surgical resection, ablation, or stereotactic radiotherapy. The primary endpoint was the objective response rate (ORR), and secondary endpoints included: disease control rate (DCR), R0 resection rate of liver metastases, progression-free survival (PFS), 3-year/5-year survival rates, and the incidence of acute toxicities of any grade and grades 3/4.

Study Overview

• Status: Not yet recruiting
• Conditions: Colo-rectal Cancer
• Intervention / Treatment: Drug: FULIRI combination targeted therapy

Detailed Description

Irinotecan (IRI, also known as CPT-11) is an important component in chemotherapy for metastatic colorectal cancer. It induces single-strand DNA damage and blocks DNA replication. After traditional irinotecan administration, both the parent drug and its active metabolite SN-38 exist in two forms: active lactone and carboxylate. The lactone ring structure is unstable in neutral and alkaline solutions. Under physiological pH conditions, the active lactone rapidly hydrolyzes and becomes inactive as a carboxylate, thus reducing its efficacy, which limits its clinical application. The most significant adverse events in patients receiving irinotecan treatment are diarrhea, nausea, vomiting, and neutropenia; in patients receiving irinotecan monotherapy, the main causes of treatment-related death are neutropenic infection, grade 4 diarrhea, and fatigue. Shijiazhuang Pharmaceutical Group's first generic irinotecan liposome is a new formulation that improves upon traditional irinotecan. It encapsulates the active substance irinotecan in liposomes, utilizing the enhanced permeability and retention (EPR) effect to specifically target the tumor area. This increases the affinity of the drug to cancer cells, overcomes drug resistance, reduces the dosage, improves efficacy, and reduces toxic side effects, thereby mitigating the limitations of irinotecan in clinical use.

Currently, there is a lack of research data on irinotecan liposome combined with 5-FU/LV and targeted therapy in patients with advanced metastatic colorectal cancer. Because irinotecan liposome cannot directly replace the dosage of conventional irinotecan, we are conducting a phase II clinical study for first-line conversion therapy in patients with colorectal cancer liver metastases. This study aims to explore the safety and efficacy of irinotecan liposome combined with 5-FU/LV + bevacizumab or cetuximab, thus providing more treatment options for patients with advanced metastatic colorectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yongchang Wei; Phone Number: +8617771886922; Email: weiyongchang@whu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Zhongnan Hospital of Wuhan University
      • Contact: Yongchang Wei; Phone Number: +862767812787; Email: weiyongchang@whu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

- (1) Age 18-75 years; (2) Histologically confirmed colorectal adenocarcinoma; (3) Synchronous liver metastasis of colorectal cancer, or liver metastasis occurring after curative surgery for colorectal cancer, and no prior systemic anti-tumor treatment (including but not limited to systemic chemotherapy, molecular targeted therapy, immunotherapy, biological therapy, and other investigational drugs) after diagnosis of liver metastasis; (4) Liver metastasis deemed unresectable by MDT assessment, or potentially resectable but with a CRS score ≥3; (5) For patients who have received neoadjuvant or adjuvant therapy for colorectal cancer, the date of first diagnosis of liver metastasis must be at least 6 months after the last dose of neoadjuvant or adjuvant therapy; (6) At least one measurable target lesion on CT scan, assessable according to RECIST v1.1 criteria; (7) ECOG performance status 0-2; (8) Good organ function, without severe comorbidities of the heart, liver, lungs, kidneys, brain, etc.; (9) Blood routine: HGB ≥90 g/L, WBC >3.5 × 10^9/L (NEU ≥1.5 × 10^9/L), PLT ≥90 × 10^9/L; Liver function: ALT or AST ≤2.5 times the upper limit of normal (ULN); Bilirubin ≤1.5 × ULN; Renal function: serum creatinine ≤1.5 × ULN; (10) Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days before starting the study medication and be willing to use a medically approved highly effective contraceptive method during the study and for 3 months after the last dose of study medication; male subjects with partners of childbearing potential must agree to use effective contraception during the study and for 3 months after the last dose of study medication.

(11) The subject has given informed consent and signed the informed consent form, and is willing and able to comply with the planned visits, study treatment, laboratory tests, and other study procedures.

Exclusion Criteria:

• (1) Pathological diagnosis reveals the presence of neuroendocrine tumor, squamous cell carcinoma, or adenosquamous carcinoma components; (2) Presence of conditions requiring emergency treatment, such as bowel obstruction, bowel perforation, or bleeding; (3) Presence of multiple metastases in sites other than the liver (excluding localized lung metastases (≤2) or localized retroperitoneal lymph node metastases, provided the investigator assesses that the patient has a chance of achieving NED status); (4) Patients with known microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR) who are deemed suitable for immunotherapy with immune checkpoint inhibitors by the investigator; (5) Previous treatment with irinotecan; (6) Underweight (Body Mass Index [BMI] < 18 kg/m2); (7) Concurrent or previous history of other malignancies besides cervical carcinoma in situ and basal cell carcinoma of the skin; (8) Concurrent severe infection or active pulmonary tuberculosis; (9) History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation; (10) Patients with hepatitis B, if hepatitis B DNA exceeds 1000 copies/mL, should be excluded; patients with hepatitis C, if hepatitis C RNA is positive, should be excluded; (11) Received surgery or other anti-tumor treatments (including chemotherapy, radiotherapy, investigational treatments, etc.) within 4 weeks prior to enrollment; (12) Concurrent severe gastrointestinal dysfunction (> Grade I according to NCI-CTCAE v5.0, such as intestinal inflammation or diarrhea); (13) Presence of conditions within the past 6 months that contraindicate targeted therapy, such as arterial embolism, severe bleeding, or bowel perforation (excluding bleeding caused by surgery); (14) Concurrent severe or uncontrolled systemic diseases, including but not limited to hypertension (systolic blood pressure consistently above 150 mmHg, diastolic blood pressure consistently above 95 mmHg), diabetes, heart disease, etc.; (15) Patients who cannot tolerate this study or who may be allergic to the medications used in this study; (16) Patients with cognitive impairment or co-existing severe mental disorders, who are judged by the investigator to have poor adherence to chemotherapy; or other situations deemed unsuitable for participation in clinical research by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental Group; Colorectal cancer patients with liver metastases who meet the inclusion criteria will sign an informed consent form and receive FULIRI chemotherapy combined with bevacizumab/cetuximab targeted therapy. Treatment efficacy will be assessed after every four cycles of treatment. After multidisciplinary team (MDT) discussion, a decision will be made regarding whether to proceed with surgery, ablation, stereotactic radiotherapy, or other treatments. Chemotherapy combined with targeted therapy will continue for a maximum of 12 cycles, until the possibility of curative surgery/ablation or other local treatment arises, disease progression occurs, intolerable toxicity develops, or the patient withdraws informed consent (whichever comes first). The adjuvant and maintenance treatment regimens after curative surgery or achieving NED (no evidence of disease) status will be determined by the investigator.

Drug: FULIRI combination targeted therapy; Chemotherapy regimen FULIRI: Irinotecan liposome 70 mg/m2; leucovorin CF 400 mg/m2, d1, iv drop; 5-FU 400 mg/m2, d1, iv drop; 5-FU 2400 mg/m2, d1, CIV 46-48h; repeated every 2 weeks. Combined targeted therapy: Based on tumor gene analysis results, investigators may choose to combine bevacizumab (5 mg/kg, iv drop, d1) or cetuximab (500 mg/m2, iv drop, d1), repeated every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR), also known as overall response rate or efficacy rate, refers to the proportion of patients in a clinical trial whose tumor volume shrinks to a predetermined value and remains at that level for a minimum specified duration.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	DCR refers to the percentage of patients who achieve complete remission (CR), partial remission (PR), or stable disease (SD) after receiving a certain anti-tumor treatment, out of the total number of evaluable cases.	3 years
R0 resection rate of liver metastases	The proportion of surgical patients who achieve an R0 resection. R0 resection: All gross disease has been removed, and microscopic examination reveals all surgical margins free of tumor.	1 year
Progression-free survival (PFS)	PFS is defined as the time period from the start of treatment until disease progression or death.	3 years
Overall survival (OS)	The time interval between the date of randomization to the date of death. If the patient has been alive, the time until the last follow-up is taken as the overall survival period.	3/5 years

Collaborators and Investigators

• Sponsor: Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: March 30, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; Liver metastasis; FULIRI
• 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; Colonic Neoplasms
• Other Study ID Numbers: 2025073

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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