New Second-Line Combo Therapy for MSS Metastatic Colorectal Cancer

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

• mPFS [Time frame: 42 months]

Eligibility criteria

Inclusion criteria

• 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 criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07559760 · 25K445-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗