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
The First Hospital of Jilin University
30 participants
Nov 1, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria19
- 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.
- Cardiac: LVEF ≥ 50 %.
- Voluntary written informed consent; willing and able to comply with study procedures and follow-up.
- WOCBP must have a negative serum/urine pregnancy test within 3 days before first study-dose (Cycle 1 Day 1).
- 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 Criteria22
- 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.
- HCV-seropositive allowed only if HCV RNA negative (or below LLoQ).
- 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.
- Other severe uncontrolled disorders (e.g., frequent seizures, hepatic failure).
- Other malignancies within 5 years, except adequately treated basal-cell carcinoma of skin or cervical carcinoma in situ.
- Participation in another clinical drug trial within 4 weeks or less than 5 half-lives of the previous investigational agent, whichever is longer.
- Any social or medical condition that, in the investigator's opinion, could interfere with informed consent, study participation, or interpretation of results.
- Patients deemed by the investigator to be unsuitable for enrollment.
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Interventions
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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07559760