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

September 17, 2024 updated by: Yuan-Sheng Zang, Shanghai Changzheng Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Shanghai, China, 200004
        • Recruiting
        • Shanghai Changzheng Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: 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.
Active Comparator: 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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Proportion of patients with reduction in tumor burden of a predefined amount, including complete remission and partial remission
Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival
Time Frame: From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks
Time from treatment beginning until death from any cause
From date of treatment beginning until the date of death from any cause, through study completion, an average of 8 weeks
Deepness of response
Time Frame: Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Investigation of depth of response during first-line treatment
Evaluation of tumor burden based on RECIST criteria through study completion, an average of 8 weeks
Progress Free Survival
Time Frame: Evaluation of tumor burden based on RECIST criteria until first documented progress or death through study completion, an average of 8 weeks
Time from treatment beginning until disease progression or death from any cause
Evaluation of tumor burden based on RECIST criteria until first documented progress or death through study completion, an average of 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Changzheng Hospital

Investigators

  • Principal Investigator: Yuan-Sheng Zang, Professor, Shanghai Changzheng Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2024

Primary Completion (Estimated)

August 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

September 3, 2024

First Submitted That Met QC Criteria

September 17, 2024

First Posted (Estimated)

September 19, 2024

Study Record Updates

Last Update Posted (Estimated)

September 19, 2024

Last Update Submitted That Met QC Criteria

September 17, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IMPROVEMENT-2

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Colorectal Carcinoma

Clinical Trials on FOLFIRI + Vemurafenib + Cetuximab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Zimbabwe

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe