Fractionated liposomal irinotecan with 5‑FU/LV and bevacizumab for second-line advanced colorectal cancer

Liposomal Irinotecan (II) Fractionated Dosing Combined With 5-FU/LV (FOLFIRInali-3) and Bevacizumab in Second-line Treatment of Advanced Colorectal Cancer: A Single-arm, Phase II Clinical Study

This study will test whether giving liposomal irinotecan in split doses together with 5‑FU/LV and bevacizumab helps people with advanced colorectal cancer who need a second-line treatment after oxaliplatin-based therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Cancer Institute and Hospital (Academic / other)
• Drugs / interventions: chemotherapy, bevacizumab
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07047560 on ClinicalTrials.gov

What this trial studies

This prospective, multicenter, single-arm Phase II trial gives fractionated liposomal irinotecan combined with 5‑FU/LV and bevacizumab as a second-line regimen for advanced colorectal cancer. Participants receive liposomal irinotecan 30 mg/m2 IV on Days 1 and 3, leucovorin 400 mg/m2 IV and a 5‑FU bolus of 400 mg/m2 followed by a 2400 mg/m2 continuous infusion over 46–48 hours, plus bevacizumab 5 mg/kg IV on Day 1 each cycle. Treatment continues until radiologically confirmed progression, unacceptable toxicity, start of a new antitumor therapy, withdrawal of consent, or investigator decision, with imaging every six weeks. The primary endpoint is objective response rate (ORR), and safety/tolerability will be closely monitored.

Who should consider this trial

Good fit: Adults (≥18) with pathologically confirmed advanced colorectal adenocarcinoma, ECOG 0–1, at least one measurable lesion per RECIST 1.1, and disease progression during or soon after oxaliplatin-containing first-line therapy are the intended participants.

Not a fit: Patients with poor performance status (ECOG ≥2), significant organ dysfunction, non-eligible histologies, or contraindications to bevacizumab or irinotecan are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If effective, this regimen could improve tumor response rates and delay progression for patients needing a second-line option after oxaliplatin-based therapy.

How similar studies have performed: Standard second-line care commonly uses irinotecan-based regimens (FOLFIRI ± bevacizumab), but the use of fractionated liposomal irinotecan is a relatively novel approach with limited prior clinical data.

Eligibility criteria

Inclusion Criteria:

1. Signed the informed consent；
2. Male or female patients ≥18 years old;
3. ECOG physical status score is 0 or 1;
4. Patients with pathologically confirmed advanced colorectal carcinoma (all other histological types excluded);
5. Patients who experienced disease progression under either of the following circumstances:During or within 6 months after first-line oxaliplatin-containing chemotherapy, or within 1 year after completing oxaliplatin-based adjuvant chemotherapy post-resection;
6. Expected survival time ≥ 3 months;
7. Patients must have at least one measurable metastatic lesion according to RECIST version 1.1;
8. Normal organ function:

   1. Hematology :Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); Platelet count ≥ 100 × 109/L (100000/mm3); Hemoglobin ≥ 90g/L;
   2. Kidney:The calculated value of creatinine clearance rate (CrCl) is ≥ 50 mL/min; Normal urine routine, urine protein\<2+or 24-hour (h) urine protein quantification\<1.0 g;
   3. Liver:Total serum bilirubin (TBiL) ≤ 1.5 × ULN;AST and ALT ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT can be ≤ 5 × ULN;Serum albumin (ALB) ≥ 30g/L;
   4. Normal coagulation function, international standardized ratio (INR) ≤ 1.5 x ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN;
9. Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; For males, surgical sterilization or agreement to use appropriate methods of contraception during observation and within 8 weeks after the last administration of study medication should be considered;
10. Comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study;

Exclusion Criteria:

1. History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ);
2. Participation in other drug trials within 4 weeks prior to enrollment;
3. Uncontrolled hypertension (SBP \>160 mmHg or DBP \>100 mmHg);
4. Acute coronary syndrome (including MI/unstable angina) with coronary angioplasty/stent placement within 6 months;
5. NYHA class II+ heart failure, unstable angina, MI, or severe arrhythmia with cardiovascular impairment within 6 months;
6. Symptomatic brain metastases;
7. Severe comorbidities requiring hospitalization (e.g., ileus, bowel obstruction, pulmonary fibrosis, refractory diabetes, heart/kidney/liver failure, psychiatric/cerebrovascular disorders);
8. Gastrointestinal perforation/fistula, intra-abdominal abscess, or non-GI fistula within 6 months;
9. Concomitant use of strong CYP3A4/CYP2C8 inhibitors/inducers or UGT1A1 inhibitors within 2 weeks;
10. Pregnancy or lactation;
11. Other investigator-determined contraindications.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Ting Deng, MD

Conditions Colorectal Cancer; Liposomal irinotecan; colorectal cancer; fractionated dosing