Comparing two chemotherapy approaches for unresectable colorectal cancer with liver metastases

FOLFOX Via Hepatic Artery Infusion Chemotherapy (HAI) Plus Systemic Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Patients With Initially Unresectable RAS-mutated Colorectal Cancer With Liver Metastases: A Prospective, Randomized, Controlled Clinical Study

This study is testing two different chemotherapy methods for patients with colorectal cancer that has spread to the liver to see which one helps them feel better and live longer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 194 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: chemotherapy, bevacizumab
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT05727163 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of FOLFOX hepatic artery infusion chemotherapy combined with intravenous irinotecan, with or without bevacizumab, against systemic intravenous FOLFOXIRI with or without bevacizumab in patients with initially unresectable RAS-mutated colorectal cancer that has spread to the liver. The study aims to determine the objective remission rate and assess various secondary outcomes such as surgical resection rates and overall survival. Patients will receive treatment every 14 days for a maximum of 12 cycles, depending on their response and tolerance to the therapy.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed RAS-mutated colorectal adenocarcinoma and unresectable liver metastases.

Not a fit: Patients with extrahepatic metastases or those who have previously received treatment for liver metastases 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 unresectable colorectal cancer liver metastases.

How similar studies have performed: Other studies have explored similar chemotherapy approaches, but this specific combination and methodology may offer novel insights into treatment efficacy.

Eligibility criteria

Inclusion Criteria:

1. Histologically confirmed colorectal adenocarcinoma
2. Imaging or pathological confirmation of liver metastases
3. The multidisciplinary team determined that the liver metastases were unresectable, defined as (i) ≥5 metastases; (ii) inability to perform R0 resection; (iii) insufficient volume of liver expected to remain after resection; (iv) failure to preserve all 3 hepatic veins after resection, failure to ensure that blood flow to and from the liver and bile ducts can be preserved, and failure to preserve 2 adjacent liver segments. If any of the above criteria are met, it can be considered as initially unresectable liver metastases.
4. Patients with mutated RAS and BrafV600E
5. No previous treatment for liver metastases, including chemotherapy, surgery, radiotherapy, transarterial chemoembolization (TACE) and targeted therapy
6. No extrahepatic metastases confirmed by CT, MRI, or PET/CT (if necessary) (consider enrollment if there is a lung or lymph node lesion less than 10 mm and metastases are difficult to identify)
7. Normal hematological function (platelets \>90×109/L; white blood cells \>3×109/L; neutrophils \>1.5×109/L)
8. Serum bilirubin ≤ 1.5 times the upper limit of normal value (ULN), transaminases ≤ 5 times ULN
9. No ascites, normal coagulation function, albumin ≥35g/L
10. Liver function Child-Push grade A
11. Serum creatinine less than upper limit of normal (ULN) or calculated creatinine clearance \>50 ml/min (using Cockcroft-Gault formula)
12. ECOG score 0-1
13. Life expectancy \> 3 months
14. Signed written informed consent

Exclusion Criteria (Patients meeting any of the following criteria will be excluded from the study):

1. Presence of any extrahepatic metastases and/or primary tumor not amenable to radical surgical resection
2. Development of liver metastases within 1 year after completion of adjuvant chemotherapy with FOLFOX or XELOX
3. Severe arterial embolism or ascites
4. Bleeding tendency or coagulation disorder
5. Hypertensive crisis or hypertensive encephalopathy
6. Severe uncontrolled systemic complications such as infections or diabetes mellitus
7. Clinically significant cardiovascular disease such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medication, unstable angina pectoris, congestive heart failure (NYHA class 2-4), arrhythmias requiring medication
8. History or physical examination revealing a central nervous system disease (e.g., primary brain tumor, epilepsy not manageable by standard therapy, presence of brain metastases, or history of stroke)
9. Previous malignancy within the last 5 years (except post-radical surgery basal cell carcinoma of the skin and/or carcinoma in situ of the cervix)
10. Treatment using any investigational drug within the last 28 days prior to the study
11. Any residual toxicity from prior chemotherapy (except alopecia), such as peripheral neuropathy ≥ NCI CTC v3.0 grade 2, will not be considered for treatment with oxaliplatin-containing regimens
12. History of allergy to any of the drugs in the study
13. Women of childbearing potential (\<2 years after last menstruation) or men of childbearing potential who are not using or have refused to use an effective non-hormonal contraceptive (IUD, barrier method combined with spermicidal gel or sterilization) during pregnancy and lactation
14. Unable or unwilling to comply with the study protocol
15. Presence of any other disease, dysfunction due to metastatic lesions, or suspicious medical findings that suggest a possible contraindication to the use of the study drug or that would place the patient at risk of treatment-related complications

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Li Yuhong

Conditions: Colorectal Cancer Metastatic, Colorectal liver metastasis, Hepatic Artery Infusion Chemotherapy, RAS-mutation, Systemic Chemotherapy, FOLFOX, FOLFOXIRI, Initially unresectable colon cancer