Clinical trial NCT06763029: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Keywords: Colorectal cancer
Irinotecan liposomes
BRAF V600E mutation
Vermofenib
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2025-01-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single-center, single-arm, prospective study
Primary purpose: TREATMENT

Brief summary: 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

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.

Primary outcomes:
measure: Objective response rate
timeFrame: The evaluation period was up to 24 months from the date the participant entered the clinical study and started the medication
Secondary outcomes:
measure: Progression free survival
timeFrame: 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
measure: Overall survival
timeFrame: 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
measure: Adverse event
timeFrame: Incidence and severity of adverse events in treatment regimens up to 24 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Affiliated Cancer Hospital of Fudan University
name: Wenhua Li, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: