FOLFOX Via HAI Plus Intravenous Irinotecan With or Without Bevacizumab Versus Systemic FOLFOXIRI With or Without Bevacizumab in Initially Unresectable RAS-mutated CRLM Patients

Launched by SUN YAT-SEN UNIVERSITY · Feb 3, 2023

Keywords

ClinConnect Summary

This clinical trial is looking to find out how effective a specific combination of treatments is for patients with RAS-mutated colorectal cancer that has spread to the liver and can't be surgically removed. The study compares two treatment approaches: one involves delivering chemotherapy directly to the liver along with a systemic chemotherapy drug and a medication called bevacizumab, while the other uses a combination of two systemic chemotherapy drugs with or without bevacizumab. The goal is to see which approach helps patients achieve better remission rates, meaning a reduction or disappearance of cancer.

To participate in this trial, patients need to have a confirmed diagnosis of colorectal cancer that has spread to the liver, with specific characteristics that make the liver tumors unresectable (unable to be surgically removed). This includes having multiple metastases or tumors that cannot be safely removed due to various medical reasons. Participants should not have received any previous treatment for their liver metastases and must meet certain health criteria, such as having normal blood counts and liver function. If eligible, participants can expect to receive one of the two treatment combinations and will be monitored closely throughout the trial. It's important to discuss any potential concerns or questions with a healthcare provider before enrolling.

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ALL

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