New Second-Line Combo Therapy for MSS Metastatic Colorectal Cancer

NCT07559760 | Recruiting Phase 2

• 1 other identifier: 25K445-001
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

Experimental Arm

EXPERIMENTAL

Treatment Regimen Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab 1. Irinotecan HCl liposome 70 mg/m² IV over 90 min, Day 1, every 2 weeks * UGT1A1\*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. 2. 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. 3. Targeted agent (physician's choice): * Bevacizumab 5 mg/kg IV, Day 1, every 2 weeks, or * Cetuximab 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

Interventions

Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab DRUG

Levofolinic Acid + 5-FU continuous infusion + irinotecan HCl liposome ± cetuximab/bevacizumab 1. Irinotecan HCl liposome 70 mg/m² IV over 90 min, Day 1, every 2 weeks * UGT1A1\*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. 2. 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. 3. Targeted agent (physician's choice): * Bevacizumab 5 mg/kg IV, Day 1, every 2 weeks, or * Cetuximab 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.

Experimental Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged 18-75 years.
• Histologically or cytologically confirmed colorectal adenocarcinoma.
• 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.
• At least one measurable lesion by RECIST 1.1.
• ECOG performance status 0-1.
• Expected survival ≥ 3 months.
• 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.

You may not qualify if:

• Prior exposure to topoisomerase-I inhibitors or their analogues in first-line therapy.
• Documented hypersensitivity to any study drug or its excipients.
• Pregnant or breast-feeding women.
• 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).
• 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.
• Severe psychiatric or psychological disorders that could compromise compliance.
• 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.
• 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).
• 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.

Sponsors & Collaborators

• The First Hospital of Jilin University: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Leucovorin; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Chang Wang

CONTACT

15804302610; wangchang@jlu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: April 30, 2026
• Study Start: November 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2029
• Last Updated: April 30, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)