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

NCT05727163 | Recruiting Phase 2

• 1 other identifier: New Triumph
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, randomized, controlled clinical study aims to evaluate the objective remission rate of FOLFOX hepatic artery infusion chemotherapy (HAI) in combination with systemic irinotecan with or without bevacizumab versus systemic intravenous FOLFOXIRI with or without bevacizumab in initially unresectable RAS-mutated colorectal cancer patients with liver metastases.

Conditions

Colorectal Cancer Metastatic

Keywords

Colorectal liver metastasis; Hepatic Artery Infusion Chemotherapy; RAS-mutation; Systemic Chemotherapy; FOLFOX; FOLFOXIRI; Initially unresectable colon cancer

Outcome Measures

Primary Outcomes (1)

• Objective Remission Rate (ORR)

  As assessed by the investigators using RECIST v1.1 criteria

  Assessed up to 48 months

Secondary Outcomes (7)

• Depth of Response (DpR)

  Assessed up to 48 months

• R0 surgical resection rate

  Assessed up to 48 months

• No evidence of disease rate (NED)

  Assessed up to 48 months

• Progression Free Survival (PFS)

  Assessed up to 48 months

• Overall Survival (OS)

  Assessed up to 48 months

Study Arms (2)

HAI group

EXPERIMENTAL

FOLFOX given via Hepatic Artery Infusion (HAI) in Combination With intravenous Irinotecan With or Without Bevacizumab. Dexamethasone 25 mg via HAI (Pre-chemotherapy) Anisodamine (654-2) 10 mg HAI (Pre-chemotherapy) Oxaliplatin 85 mg/m2 via HAI over 3 hours Leucovorin 200 mg/m2 via HAI FU 400 mg/m2 via HAI FU 2.4g/m2 via HAI over 48 hours Irinotecan 150 mg/m2 intravenously Bevacizumab 5 mg/kg intravenously The above regimen was given on Day 1 and repeated after 14 days. Patients will typically receive a maximum of 12 courses (preoperative and/or postoperative) unless disease progression is detected, intolerable adverse effects, or the patient refuses further treatment.

Drug: Dexamethasone; Drug: Anisodamine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil; Drug: Irinotecan; Drug: Bevacizumab

Systemic Chemotherapy group

ACTIVE COMPARATOR

Systemic FOLFOXIRI With or Without Bevacizumab Irinotecan 150mg/m2 intravenously Oxaliplatin 85 mg/m2 intravenously over 3 hours Leucovorin 200 mg/m2 intravenously FU 400 mg/m2 intravenously 5-FU 2400 mg/m2 continuous intravenous infusion over 46 hours Bevacizumab 5 mg/kg intravenously Note: (UGT\*28 7/7, UGT\*6 A/A, UGT\*28 6/7 and UGT\*6 A/G patients, Irinotecan dosage was reduced to 130 mg/m2) The above regimen was given on Day 1 and repeated after 14 days. Patients will typically receive a maximum of 12 courses (preoperative and/or postoperative) unless disease progression is detected, intolerable adverse effects, or the patient refuses further treatment.

Drug: Irinotecan; Drug: Bevacizumab; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Fluorouracil

Interventions

Dexamethasone DRUG

25mg via HAI (Pre-chemotherapy)

HAI group

Anisodamine DRUG

10 mg via HAI (Pre-chemotherapy)

Also known as: 654-2

HAI group

Oxaliplatin DRUG

85 mg/m2 via HAI over 3 hours

HAI group

Leucovorin DRUG

200 mg/m2 via HAI

HAI group

Fluorouracil DRUG

400 mg/m2 via HAI and 2.4g/m2 via HAI over 48 hours

Also known as: FU

HAI group

Irinotecan DRUG

150 mg/m2 intravenously

HAI group; Systemic Chemotherapy group

Bevacizumab DRUG

5 mg/kg intravenously

HAI group; Systemic Chemotherapy group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed colorectal adenocarcinoma
• Imaging or pathological confirmation of liver metastases
• 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.
• Patients with mutated RAS and BrafV600E
• No previous treatment for liver metastases, including chemotherapy, surgery, radiotherapy, transarterial chemoembolization (TACE) and targeted therapy
• 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)
• Normal hematological function (platelets \>90×109/L; white blood cells \>3×109/L; neutrophils \>1.5×109/L)
• Serum bilirubin ≤ 1.5 times the upper limit of normal value (ULN), transaminases ≤ 5 times ULN
• No ascites, normal coagulation function, albumin ≥35g/L
• Liver function Child-Push grade A
• Serum creatinine less than upper limit of normal (ULN) or calculated creatinine clearance \>50 ml/min (using Cockcroft-Gault formula)
• ECOG score 0-1
• Life expectancy \> 3 months
• Signed written informed consent

You may not qualify if:

• Presence of any extrahepatic metastases and/or primary tumor not amenable to radical surgical resection
• Development of liver metastases within 1 year after completion of adjuvant chemotherapy with FOLFOX or XELOX
• Severe arterial embolism or ascites
• Bleeding tendency or coagulation disorder
• Hypertensive crisis or hypertensive encephalopathy
• Severe uncontrolled systemic complications such as infections or diabetes mellitus
• 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
• 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)
• 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)
• Treatment using any investigational drug within the last 28 days prior to the study
• 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
• History of allergy to any of the drugs in the study
• 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
• Unable or unwilling to comply with the study protocol
• 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

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Interventions

Dexamethasone; anisodamine; 2-(phenylmethyl)-1-naphthol; Oxaliplatin; Leucovorin; Fluorouracil; Irinotecan; Bevacizumab

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Camptothecin; Alkaloids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Li Yuhong

CONTACT

020-87342487; liyh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: February 14, 2023
• Study Start: July 29, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 30, 2025

Record last verified: 2025-05

Locations

CN (1)