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

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-01
• Study Completion Date: 2026-12-31

Brief 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.

Conditions

Colorectal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FOLFIRI + Vemurafenib + Cetuximab

Experimental Group: 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.

Group Type: EXPERIMENTAL

FOLFIRI + Vemurafenib + Cetuximab

Intervention Type: DRUG

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.

FOLFIRI ± Bevacizumab

Control Group: 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.

Group Type: ACTIVE_COMPARATOR

FOLFIRI ± Bevacizumab

Intervention Type: DRUG

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.

Interventions

FOLFIRI + Vemurafenib + Cetuximab

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.

Intervention Type: DRUG

FOLFIRI ± Bevacizumab

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.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Changzheng Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yuan-Sheng Zang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yuan-Sheng Zang, Professor

Role: PRINCIPAL_INVESTIGATOR

Shanghai Changzheng Hospital

Locations

Shanghai Changzheng Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Zhan Wang, Professor

Role: CONTACT

13916229609@139.com

86-13916229609

Facility Contacts

Zang Wang, Professor

Role: primary

13916229609@139.com

8613916229609

Other Identifiers

IMPROVEMENT-2

Identifier Type: -

Identifier Source: org_study_id