Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced Colorectal Cancer

Official title

Phase II Exploratory Study of Irinotecan Liposomes Combined with Cetuximab + Vermofenib in First-line Failure of Advanced RAS Wild /BRAF Mutated Colorectal Cancer

Overview

Efficacy and safety of irinotecan liposomes combined with cetuximab + vermofenib in first-line failure of advanced RAS wild /BRAF mutated colorectal cancer, Exploratory analysis of biomarkers (including but not limited to ctDNA, immune microenvironment indicators, tumor mutation load, lymphocyte subsets, cytokines, gut microbes, and others) in relation to efficacy.

Detailed description

This study aims to explore the following key questions: 1) whether replacing ordinary irinotecan in VIC protocol with irinotecan liposomes can improve the safety and efficacy of BRAF V600E mutation in second-line treatment of metastatic colorectal cancer; 2) To provide a reference for identifying the dominant population for the benefit of irinotecan liposomes through the exploration of a range of biomarkers (including but not limited to ctDNA, immune microenvironmental indicators, tumor mutation load, lymphocyte subsets, cytokines, gut microbes, and others). Thus, it provides more treatment options for BRAF V600E mutations in patients with metastatic colorectal cancer

Interventions

• Drug Irinotecan liposomes combined with cetuximab + vermofenib
  Vermofenil 960mg orally twice daily; Irinotecan liposomes, 70mg/m2, d1, 90 min intravenously, Q2W; Cetuximab 500mg/m2, d1, Q2W;

Primary outcome measures

• Objective response rate [Time frame: The evaluation period was up to 24 months from the date the participant entered the clinical study and started the medication]

Secondary outcome measures (3)

• Progression free survival [Time frame: The evaluation period was up to 24 months from the date of the subject's first medication to the date of first recorded progress or the date of death from any cause, whichever came first]
• Overall survival [Time frame: The evaluation period was up to 24 months from the date of the subject's first medication to the date of death from any cause]
• Adverse event [Time frame: Incidence and severity of adverse events in treatment regimens up to 24 months]

Eligibility criteria

Inclusion criteria

• at least 18 years of age;
• Colorectal adenocarcinoma was confirmed by histological or cytopathological examination, and RAS wild /BRAF V600E mutation was detected by PCR or NGS;
• Failure or intolerance of standard first-line treatment. First-line regimens including oxaliplatin and/or irinotecan in combination with fluorouracil in patients with MSS; For BRAF V600E mutated patients with MSI-H, first-line immunotherapy with PD-1 or PD-L1 is required;
• At least one measurable lesion according to RECIST v1.1;
• ECOG score is 0\~2;
• Good bone marrow and organ function: ① Neutrophils (ANC) ≥1.5×109/L, platelets (PLT) ≥100×109/L, hemoglobin (Hb) ≥90g/L, white blood cells (WBC) ≥3.0×109/L, albumin (ALB) ≥32 g/L, and no bleeding tendency; ② AST, ALT and alkaline phosphatase (ALP) were all ≤2.5× upper limit of normal range (ULN), and ≤5×ULN when liver metastases occurred; Total bilirubin ≤1.5×ULN; Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance ≥60 ml/min (calculated according to Cockroft-Gault);
• Expected survival ≥3 months;
• Can understand the situation of this study, patients and (or) legal representatives voluntarily agree to participate in this study and sign informed consent.

Exclusion criteria

• Patients who have previously received BRAF inhibitors or irinotecan liposomes;
• Proven allergic to the test drug and/or its excipients;
• symptomatic, untreated brain metastases or meningeal metastases that fail to achieve clinical stability;
• Acute or subacute intestinal obstruction or chronic inflammatory bowel disease;
• have had other malignant tumors within the past 5 years or currently, except for cured cervical carcinoma in situ, uterine carcinoma in situ and non-melanoma skin cancer;
• Pregnant or lactating female patients, patients of childbearing age who refuse to accept contraceptive measures;
• Patients considered by the investigator to be unsuitable for this study.

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

• Fudan University Shanghai Cancer Center — Shanghai

Identifiers

NCT: NCT06763029 · FudanU.2411307-18

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗