Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer

Trial Title: Irinotecan Hydrochloride Liposome Injection (Ⅱ) Combined with Fluorouracil, Folinic Acid, Vermofenib and Cetuximab in First-line Treatment of BRAFV600E Mutated Advanced Colorectal Cancer

NCT ID: NCT06603376

Condition: Colorectal Carcinoma

Conditions: Official terms:
Colorectal Neoplasms
Bevacizumab
Cetuximab
Vemurafenib

Conditions: Keywords:
colorectal cancer
BRAF V600E
chemotherpay
Vemurafenib
Cetuximab
irinotecan hydrochloride liposome injection

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Double (Participant, Investigator)

Intervention:

Intervention type: Drug
Intervention name: FOLFIRI + Vemurafenib + Cetuximab
Description: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Cetuximab: 500 mg/m², intravenous infusion over at least 2 hours, on day 1; Vemurafenib: 720 mg, orally twice daily. Repeat every 2 weeks.
Arm group label: FOLFIRI + Vemurafenib + Cetuximab

Intervention type: Drug
Intervention name: FOLFIRI ± Bevacizumab
Description: Liposomal Irinotecan Hydrochloride Injection (II): 60 mg/m², intravenous infusion over at least 90 minutes, on day 1; Leucovorin: 400 mg/m², intravenous infusion over 2 hours, on day 1; 5-FU: 400 mg/m², intravenous bolus; 5-FU: 2400 mg/m², continuous infusion over 46-48 hours, on day 1; Bevacizumab: 5 mg/kg, intravenous infusion, on day 1. Repeat every 2 weeks.
Arm group label: FOLFIRI ± Bevacizumab

Summary: Based on the upstream signaling features of BRAFV600E and the bypass feedback mechanisms, considering the pro-apoptotic effects of chemotherapy and the synergistic effects of targeted therapy, previous IMPROVEMENT trial creatively explored a balanced chemotherapy-targeted combination approach (FOLFIRI + Vemurafenib + Cetuximab) in advanced colorectal cancer patients with BRAF V600E mutaiton using a signle-arm study design, demonstrating significant therapeutic efficacy in these patietns . To further validate the effectiveness and safety of this regimen and to solidify its clinical value, it is crucial to conduct a randomized, controlled trial. Investigators plan to use the current standard regimen as a control to compare this strategy (FOLFIRI + Vemurafenib + Cetuximab) on a large cohort of patients with BRAFV600E-mutant advanced colorectal cancer in the first-line setting, focusing on its efficacy and safety.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Patients with advanced colorectal adenocarcinoma confirmed by histology or cytology. - Patients with BRAFV600E mutation confirmed by tissue or blood testing. - Patients who have not received systemic therapy or who have experienced metastasis or recurrence 12 months after completing adjuvant therapy. - Patients must have at least one measurable lesion according to RECIST 1.1 criteria. - Patients who received local radiotherapy at least 3 weeks before the first drug treatment are allowed to enroll, but lesions evaluated by RECIST should not be within the radiation field. - Patients aged ≥18 years and ≤80 years. - ECOG performance status of 0-2. - Expected survival of ≥12 weeks. - Patients must have the ability to understand and voluntarily sign a written informed consent. - Women of childbearing potential must have a negative pregnancy test within 7 days prior to the start of treatment. During the study, both the patient and their partner must use contraception. Exclusion Criteria: - Patients who have undergone major surgery or suffered severe trauma within 4 weeks prior to the first dose of the study drug. - Patients with hypersensitivity to any component of the study regimen. - Patients who are planning to conceive or are already pregnant. - Patients with brain metastases who cannot accurately describe their condition. - Patients with the following conditions within 6 months prior to the start of the study treatment: myocardial infarction, severe/unstable angina, congestive heart failure greater than NYHA Class 2, uncontrolled arrhythmias, etc. - Abnormal laboratory test results: - Absolute neutrophil count (ANC) <1,500/mm³; - Platelet count <75,000/mm³; - Total bilirubin >1.5 times the upper limit of normal (ULN); ALT (alanine aminotransferase) and AST (aspartate aminotransferase) >2.5 times ULN (for patients with liver metastasis >5 times ULN); Creatinine >1.5 times ULN; - Patients who have had any cancer other than advanced colorectal cancer within five years prior to the start of the study treatment. Exceptions include cervical carcinoma in situ, cured basal cell carcinoma, and bladder epithelial tumors. - Patients with a history of drug abuse, substance abuse, or alcohol dependence. - Patients who are legally incapacitated or have limited civil capacity. - Any other conditions deemed unsuitable for enrollment by the investigator.

Gender: All

Minimum age: 18 Years

Maximum age: 80 Years

Healthy volunteers: No

Locations:

Facility:
Name: Shanghai Changzheng Hospital

Address:
City: Shanghai
Zip: 200004
Country: China

Status: Recruiting

Contact:
Last name: Zang Wang, Professor

Phone: 8613916229609
Email: 13916229609@139.com

Start date: September 1, 2024

Completion date: December 31, 2026

Lead sponsor:
Agency: Shanghai Changzheng Hospital
Agency class: Other

Source: Shanghai Changzheng Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06603376