Liposomal Irinotecan and Leucovorin/5-fluorouracil Plus Bevacizumab in Metastatic Colorectal Cancer

Official title

Liposomal Irinotecan + Leucovorin + 5-fluorouracil + Bevacizumab as Second-line Therapy in Metastatic Colorectal Cancer (IRIS)：a Multicenter, Single-arm, Prospective, Phase II Study

Overview

This is a multi-center, single-arm study to investigate the efficacy and safety of liposomal irinotecan+5-FU/LV+ bevacizumab as second-line therapy in metastatic colorectal cancer in Chinese population.

Detailed description

Colorectal cancer (CRC) has a poor prognosis and poses a serious threat to human health. FOLFIRI (irinotecan+5-FU/LV) / FOLFOX (oxaliplatin+5-FU/LV) ± angiogenesis inhibitors are common treatments for advanced CRC. For patients receiving oxaliplatin-based therapy, irinotecan-based therapy is recommended as second-line therapy. Liposomal irinotecan is a new pharmaceutical form of traditional irinotecan. It adopts a special loading technology to encapsulate traditional irinotecan in liposomes, which can avoid its hydrolysis under physiological conditions, increase the affinity with cancer cells, overcome drug resistance, increase the drug uptake by cancer cells, reduce the drug dose, improve the efficacy and reduce the toxic side effects. The aim of this study is to explore the efficacy and safety of liposomal irinotecan+5-FU/LV + bevacizumab as second-line treatment for metastatic CRC.

Interventions

• Drug liposomal irinotecan
  liposomal irinotecan 70 mg/m²
• Drug 5-FU
  5-FU 2400 mg/m²
• Drug LV
  5-FU 2400 mg/m²
• Drug Bevacizumab
  bevacizumab 5 mg/kg

Primary outcome measures

• Objective Response Rate [Time frame: 4 months]

Secondary outcome measures (5)

• Disease Control Rate [Time frame: 4 months]
• Duration of Response [Time frame: 4 months]
• Progress-free survival [Time frame: 6 months]
• Overall survival [Time frame: 1 year]
• Incidence of adverse events [Time frame: 5 months]

Eligibility criteria

Inclusion criteria

• Age: 18-75 years old.
• Histologically or cytologically proven colon or rectum adenocarcinoma.
• Confirmed as unresectable metastatic disease through radiological examination.
• At least one measurable lesion (according to RECIST v1.1).
• First-line treatment with oxaliplatin-based therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 \~ 2.
• The expected survival time ≥3 months.
• Subject has adequate biological parameters as demonstrated by the following: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥100×10\^9/L, hemoglobin (Hgb) ≥90 g/L, white blood cell (WBC)≥3.0×10\^9/L.
• Adequate hepatic function as evidenced by total bilirubin ≤1.5 × upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) ≤2.5 x ULN, ≤5 x ULN if liver metastases are present.
• Adequate renal function as evidenced by serum creatinine (Cr)≤1.5 x ULN or creatinine clearance ≥60 mL/min, proteinuria \<2+.
• Normal coagulation function (INR≤1.5).
• Agree and be able to comply with the plan during the study period. Provide written informed consent before entering the study screening.

Exclusion criteria

• Any other malignancy within 5 years prior to randomization, with the exception of cured in-situ carcinoma or basal cell carcinoma.
• Previous treatment with irinotecan/liposomal irinotecan.
• MSI-H/dMMR
• Massive pleural effusion or ascites requiring intervention.
• Active, uncontrolled bacterial, viral, or fungal infections that require systemic treatment.
• Active HIV, HBV, HCV infection.
• Combined with uncontrollable systemic diseases.
• Presence of severe gastrointestinal disease (including active bleeding, \> grade 1 obstruction , \> grade 1 diarrhea or gastrointestinal perforation)
• History of laparotomy, thoracotomy, or intestinal resection within 28 days before enrolment.
• Presence of interstitial pneumonia or pulmonary fibrosis.
• Allergy to or intolerance to therapeutic drugs or their excipients;.
• History of pulmonary hemorrhage/hemoptysis ≥ Grade 2 (defined as bright red blood of at least 2.5mL) within one month prior to enrollment.
• Presence of arterial embolism, severe bleeding (excluding bleeding caused by surgery) or tendency for existing embolism or severe bleeding within 6 months before enrollment.
• Patients with symptomatic central nervous system metastases.
• Documented serum albumin ≤3 g/dL
• Use of strong inhibitors or inducers of CYP3A, CYP2C8 and UGT1A1.
• Pregnant or breastfeeding women, or subjects of childbearing age who refuse contraception.
• Participated in other trial within 30 days prior to the first dose of study treatment.
• Patients who had received any intravenous antineoplastic therapy within 28 days or oral antineoplastic therapy within 14 days before the first dose of study drug
• Patients who are not suitable to participate in this trial for any reason judged by the investigator.

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 Fourth Hospital of Hebei Medical University — Shijiazhuang

Identifiers

NCT: NCT06184698 · CSPC-DEY-CRC-K04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗