New Second-Line Combo Therapy for MSS Metastatic Colorectal Cancer

A Prospective Study of Levoleucovorin/5-FU Co-Infusion Combined With Liposomal Irinotecan ±Cetuximab/Bevacizumab as Second-Line Therapy for MSS Metastatic Colorectal Cancer

This is a single-center, single-arm study designed to evaluate the efficacy and safety of second-line treatment in patients with advanced colorectal cancer (those who have progressed on or are intolerant to first-line oxaliplatin-based regimens with or without targeted therapy) receiving Levofolinic Acid + 5-FU continuous infusion combined with irinotecan hydrochloride liposome ± cetuximab/bevacizumab. Approximately 30 patients will be enrolled.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Drug: Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chang Wang; Phone Number: 15804302610; Email: wangchang@jlu.edu.cn

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • The First Hospital of Jilin University
      • Contact: Chang Wang; Phone Number: 15804302610; Email: wangchang@jlu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female, aged 18-75 years.
2. Histologically or cytologically confirmed colorectal adenocarcinoma.

3. Unresectable, MSS-type metastatic colorectal cancer that has failed or is intolerant to first-line standard oxaliplatin plus fluoropyrimidine ± targeted therapy.

   • Failure definition: progression during or within 3 months after completing first-line oxaliplatin/fluoropyrimidine ± targeted therapy.
   • Adjuvant setting: progression/recurrence during or within 6 months of completing adjuvant oxaliplatin-based chemotherapy/chemoradiation counts as first-line failure.
4. At least one measurable lesion by RECIST 1.1.
5. ECOG performance status 0-1.
6. Expected survival ≥ 3 months.

7. Adequate organ function within 14 days before enrollment (no transfusion or growth-factor support):

   • Hematology: Hb ≥ 90 g/L; WBC ≥ 3.0 × 10⁹/L; ANC ≥ 1.5 × 10⁹/L; PLT ≥ 90 × 10⁹/L.
   • Coagulation: INR ≤ 1.5 × ULN; APTT ≤ 1.5 × ULN (stable anticoagulation at therapeutic range allowed).
   • Renal: Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault).
   • Hepatic:
   • No liver mets: TBIL ≤ 1.5 × ULN, ALT ≤ 2.5 × ULN, AST ≤ 2.5 × ULN.
   • Liver mets: TBIL ≤ 2 × ULN, ALT ≤ 5 × ULN, AST ≤ 5 × ULN.
   • Cardiac: LVEF ≥ 50 %.
8. Voluntary written informed consent; willing and able to comply with study procedures and follow-up.
9. WOCBP must have a negative serum/urine pregnancy test within 3 days before first study-dose (Cycle 1 Day 1).
10. All subjects (men and women) with reproductive potential must use a highly effective contraceptive method (annual failure rate < 1 %) from screening until 120 days after the last dose of investigational product or 180 days after the last chemotherapy dose, whichever is later.

Exclusion Criteria:

1. Prior exposure to topoisomerase-I inhibitors or their analogues in first-line therapy.
2. Documented hypersensitivity to any study drug or its excipients.
3. Pregnant or breast-feeding women.
4. Toxicities from prior therapy not resolved to CTCAE v5.0 Grade ≤ 1 (except alopecia or other toxicities deemed by the investigator to pose no safety risk).
5. Any anti-cancer therapy (chemotherapy, radiotherapy, biologics, targeted therapy, immunotherapy, etc.) within 4 weeks before first study-dose; major surgery (excluding biopsy) within 4 weeks that has not fully healed.
6. Severe psychiatric or psychological disorders that could compromise compliance.

7. Clinically significant cardiovascular disease:

   • Severe/unstable angina, symptomatic congestive heart failure (NYHA ≥ II), clinically significant arrhythmia requiring treatment, arterial thrombosis, acute coronary syndrome, MI, cerebrovascular accident (including TIA) or other Grade ≥ 3 CV event within 6 months prior to first dose.
   • QTcF ≥ 450 ms (men) or ≥ 470 ms (women) on resting 12-lead ECG.

8. Infection-related:

   • Active infection or unexplained fever > 38.5 °C on screening or dosing day (tumor fever allowed at investigator's discretion).
   • Serious infection (CTCAE Grade 3, e.g., pneumonia, bacteremia) requiring hospitalization within 4 weeks.
   • Active pulmonary inflammation on baseline imaging or need for systemic antibiotics (prophylactic antibiotics permitted).

9. Known HIV-positive, active hepatitis B, or hepatitis C:

   • HBsAg or HBcAb positive: HBV DNA must be ≤ 2.5 × 10³ copies/mL (or ≤ 500 IU/mL, or below LLoQ); HBsAg(+) subjects must receive anti-HBV prophylaxis throughout study treatment.
   • HCV-seropositive allowed only if HCV RNA negative (or below LLoQ).
10. History or current evidence of leptomeningeal metastases. Active brain metastases: untreated and/or symptomatic, or requiring corticosteroids or anticonvulsants. Subjects treated with surgery or radiotherapy may enter if imaging ≥ 4 weeks shows stable CNS disease, symptoms have resolved, no corticosteroids for ≥ 2 weeks, and acute toxicities have recovered.
11. Other severe uncontrolled disorders (e.g., frequent seizures, hepatic failure).
12. Other malignancies within 5 years, except adequately treated basal-cell carcinoma of skin or cervical carcinoma in situ.
13. Participation in another clinical drug trial within 4 weeks or less than 5 half-lives of the previous investigational agent, whichever is longer.
14. Any social or medical condition that, in the investigator's opinion, could interfere with informed consent, study participation, or interpretation of results.
15. Patients deemed by the investigator to be unsuitable for enrollment.

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 Arm; Treatment Regimen Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab; Irinotecan HCl liposome 70 mg/m² IV over 90 min, Day 1, every 2 weeksUGT1A1*28 7/7 homozygotes: start at 50 mg/m²; escalate to 70 mg/m² from cycle 2 if well tolerated.Premedication per liposomal irinotecan label.; Levofolinic Acid 200 mg/m² + 5-FU 2 400 mg/m², both placed in the same ambulatory pump and infused continuously over 46-48 h starting Day 1.; Targeted agent (physician's choice):Bevacizumab 5 mg/kg IV, Day 1, every 2 weeks, orCetuximab 500 mg/m² IV, Day 1, every 2 weeks, or 400 mg/m² first dose then 250 mg/m² weekly. Liposomal irinotecan is given for a maximum of 12 cycles until progression or unacceptable toxicity. Upon investigator decision, patients may switch to maintenance: Levofolinic Acid + 5-FU continuous infusion ± bevacizumab/cetuximab.

Drug: Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab; Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab; Irinotecan HCl liposome 70 mg/m² IV over 90 min, Day 1, every 2 weeksUGT1A1*28 7/7 homozygotes: start at 50 mg/m²; escalate to 70 mg/m² from cycle 2 if well tolerated.Premedication per liposomal irinotecan label.; Levofolinic Acid 200 mg/m² + 5-FU 2 400 mg/m², both placed in the same ambulatory pump and infused continuously over 46-48 h starting Day 1.; Targeted agent (physician's choice):Bevacizumab 5 mg/kg IV, Day 1, every 2 weeks, orCetuximab 500 mg/m² IV, Day 1, every 2 weeks, or 400 mg/m² first dose then 250 mg/m² weekly. Liposomal irinotecan is given for a maximum of 12 cycles until progression or unacceptable toxicity. Upon investigator decision, patients may switch to maintenance: Levofolinic Acid + 5-FU continuous infusion ± bevacizumab/cetuximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mPFS	median Progression Free Survival.It is defined as the time from enrollment to the date of first documented tumor progression (assessed according to RECIST 1.1 criteria, regardless of whether treatment is continued) or the date of death from any cause, whichever occurs first.	42 months

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2029

Study Registration Dates

• First Submitted: April 24, 2026
• First Submitted That Met QC Criteria: April 24, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: November 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; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Bevacizumab; Leucovorin
• Other Study ID Numbers: 25K445-001

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