FOLFOX-HAIC as Conversion Treatment for Initially Unresectable Colorectal Liver Metastasis

NCT06988852 | Recruiting Phase 2

• 1 other identifier: CHALLENGE-A1
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Try FOLFOX-HAIC combining bevacizumab or cetuximab for initially unresectable colorectal liver metastasis patients to increase the conversion to resection rate to improve long-term survival outcomes

Conditions

Colorectal Liver Metastasis (CRLM)

Outcome Measures

Primary Outcomes (1)

• conversion to resection rate

  conversion to resection rate: the number of patients underwent liver resection/total patients underwent FOLFOX-HAIC combining with target agents

  180 days

Secondary Outcomes (2)

• drug treatment safety assessment

  Baseline up to study termination, assessed up to 12 months.

• objective response rate

  From the time of enrollment until disease progression, death, or the end of the study, assessed up to 12 months.

Study Arms (1)

Treatment group

EXPERIMENTAL

Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab

Combination Product: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Procedure: hepatic arterial infusion chemotherapy (HAIC); Drug: Bevacizumab; Drug: Cetuximab (Erbitux); Procedure: liver resection

Interventions

FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]) COMBINATION_PRODUCT

The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion. The FOLFOX regimen involving oxaliplatin (130mg/m2, day 1, 0-2h), leucovorin (400 mg/m2, day 1, 2-3h), 5-Fu (400mg/m2, day 1, bolus at 3h, then 2400 mg/m2, day 1-3, 3-49h), was administered via the microcatheter. The microcatheter and sheath were removed after HAIC finished. We didn't implanted port catheter system and repeated percutaneous femoral artery puncture and catheterization once every 3

Treatment group

hepatic arterial infusion chemotherapy (HAIC) PROCEDURE

The procedures of FOLFOX-HAIC were as follows: 1) a 5 French sheath was inserted into the femoral artery by Seldinger technique, then a 3.5 French catheter entered the coeliac trunk and superior mesenteric artery to assess the feeding arteries of tumors and identify any extra-collateral vessels which may cause drug leakage. These vessels would be embolized with gelatin sponge particles or metallic coils if necessary. A 2.7 French microcatheter was selectively inserted into the left/right/proper hepatic artery then patients were transferred to inpatient ward to start chemotherapy drug infusion.

Treatment group

Bevacizumab DRUG

We would inject bevacizumab at the dose of 7.5mg/kg once every 3 weeks if the primary tumors located from right-side to splenic flexure colon or the genotype of RAS or RAF was mutational.

Treatment group

Cetuximab (Erbitux) DRUG

We would inject cetuximab at an initial dose of 400mg/m2 and maintained a dose of 250mg/m2 once every week if we didn't choose bevacizumab.

Treatment group

liver resection PROCEDURE

If patients reached potential resectable state, we would perform liver resection.

Treatment 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:

• age 18-75 years
• no history of other malignant diseases
• refuse or progress in prior systemic treatment
• diagnosed as CRLM confirmed by pathology, in spite of whether the primary tumor had been resected
• at least one lesion in the liver could be measured
• left ventricular ejection ≥45%, forced expiratory volume in one second/forced vital capacity≥60% and Eastern Cooperative Oncology Group (ECOG) score of 0-1
• Child-Pugh class A
• adequate organ function, i.e.: white blood cell (WBC) ≥3.0×109/L, neutrophils ≥1.5×109/L, platelet (PLT) ≥75×109/L, total bilirubin ≤30μmol/L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤200U/L, creatinine ≤150μmol/L

You may not qualify if:

• extra-hepatic metastasis verified by medical imaging
• unable to tolerate chemotherapy, anesthesia or surgery
• allergy or previous intolerable to any agent of oxaliplatin, leucovorin, 5-Fu, bevacizumab or cetuximab
• tumor spread in abdomen
• cerebral infarction, cerebral hemorrhage, gastrointestinal hemorrhage/perforation within 6 months, coagulation disorders and gastrointestinal ulcer
• primary tumor may not be completely resected
• prior treatment of CRLM with resection, ablation or radiation
• incomplete clinical or follow-up data

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Interventions

Folfox protocol; Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab; Cetuximab; Hepatectomy

Intervention Hierarchy (Ancestors)

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; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Digestive System Surgical Procedures; Surgical Procedures, Operative

Central Study Contacts

Zhang Bi Xiang

CONTACT

862783663400; bixiangzhang@hust.edu.cn

Study Design

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

Study Record Dates

• First Submitted: May 4, 2025
• First Posted: May 25, 2025
• Study Start: May 1, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)