Comparing two chemotherapy regimens for colorectal cancer with liver metastases

mFOLFOXIRI Plus Bevacizumab Versus mFOLFOX6 Plus Bevacizumab for the First Line Treatment of RAS Mutant Unresectable Colorectal Liver-limited Metastases

This study is testing which of two chemotherapy treatments works better for people with colorectal cancer that has spread to the liver and can't be surgically removed.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 308 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: bevacizumab, chemotherapy
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT04781270 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of two chemotherapy regimens, modified FOLFOXIRI plus bevacizumab and modified FOLFOX6 plus bevacizumab, in patients with RAS mutant unresectable colorectal cancer that has metastasized to the liver. Patients will be randomly assigned to one of the two treatment groups after confirming their eligibility based on specific mutation statuses and imaging assessments. The study aims to determine which regimen is more effective in achieving resectability of liver metastases. Regular imaging will be conducted to monitor disease status and treatment response.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with RAS mutant colorectal adenocarcinoma and initially unresectable liver-only metastases.

Not a fit: Patients with extrahepatic metastases or those who have previously received systemic treatment for metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective treatment option for patients with RAS mutant colorectal cancer and liver metastases, potentially leading to curative surgery.

How similar studies have performed: Other studies have shown promising results with similar chemotherapy regimens in treating colorectal cancer, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* Histological proof of colorectal adenocarcinoma;
* Age ≥ 18 years and ≤75 years;
* Simultaneous liver-limited metastases;
* Initially unresectable liver metastases determined by a local MDT;
* RAS mutation and BRAF V600E wild-type;
* At least one measurable liver metastasis;
* Initially resectable primary tumor or primary tumor already resected;
* World Health Organization (WHO) performance status 0-1;
* Life expectancy ≥ 3 months;
* Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
* Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
* Written informed consent.

Exclusion Criteria:

* Previous systemic treatment for metastatic disease;
* Previous surgery for metastatic disease;
* Extrahepatic metastases;
* Unresectable primary tumor;
* Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
* Acute or subacute intestinal obstruction;
* Second primary malignancy within the past 5 years;
* Drug or alcohol abuse;
* No legal capacity or limited legal capacity;
* Pregnant or lactating women;
* Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;
* Peripheral neuropathy;

Where this trial is running

Shanghai, Shanghai

• Zhongshan Hospital, Fudan University — Shanghai, Shanghai, China (RECRUITING)

Study contacts

• Principal investigator: Jianmin Xu, MD, Ph.D. — Fudan University
• Study coordinator: Jianmin Xu, MD, Ph.D.

Conditions: Colorectal Carcinoma, Liver Metastases