Clinical Efficacy of Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer

Official title

FOLFOX-Based Transarterial Infusion Chemotherapy for Unresectable Colorectal Cancer: An Open-Label, Multicenter, Randomized, Controlled, Phase Ⅱ Trial

Overview

This is a prospective, multicenter, randomized, and open-label clinical trial. It is initiated to determine the efficacy of FOLFOX-based, transarterial infusion chemotherapy (TAIC) combined with either cetuximab or bevacizumab for patients with unresectable colorectal cancer (CRC).

Detailed description

Current CRC treatment options include surgical resection, intravenous chemotherapy (IVC), radiation therapy, immunotherapy, and targeted therapy, or a combination of these options. IVC is an important therapy for CRC. Unfortunately, IVC results in broad drug distribution, while achieving with relatively low drug accumulation within the tumor. Compared with IVC, TAIC can increase the local intra-tumoral concentrations of chemotherapeutic agents by intensifying drug delivery into the tumor via super-selective catheterization of the tumor-feeding artery, and meanwhile reduce systematic toxicity. Hepatic artery infusion chemotherapy (HAIC) has been shown to yield significantly better outcomes than conventional transarterial chemoembolization (TACE) or IVC, and is now widely used for primary liver cancer and secondary liver malignancies. Based on these experiences, the investigators hypothesize that TAIC is clinically more effective at the same dose than IVC in the treatment of unresectable CRC. However, there is currently no high-quality evidence from clinical trials to support this hypothesis. To address this gap, the investigators will conduct a prospective study to verify this hypothesis. Eligible patients are those with unresectable CRC, those intolerant to surgical resection, and those with microsatellite instability or microsatellite instability low or proficient mismatch repair CRC. A total of 30 patients will be randomly assigned to the IVC group or TAIC group. Patients in the IVC group will receive the FOLFOX-based IVC with either cetuximab or bevacizumab every two weeks for a total of 8 weeks. Patients in the TAIC group will undergo FOLFOX-based TAIC combined with either cetuximab or bevacizumab on weeks 0 and 4 and will receive FOLFOX-based IVC with either cetuximab or bevacizumab on weeks 2 and 6. The primary endpoints are the objective response rate (ORR) and disease control rate (DCR).

Interventions

• Procedure Transarterial infusion chemotherapy (TAIC)
  TAIC can increase the local intra-tumoral concentrations of chemotherapeutic agents by intensifying drug delivery into the tumor via super-selective catheterization of the tumor-feeding artery, and meanwhile reduce systematic toxicity.
• Procedure Intravenous Chemotherapy（IVC）
  Intravenous administration of chemotherapeutic agents is the mainstay of chemotherapy.

Primary outcome measures

• ORR [Time frame: 8 weeks]

Secondary outcome measures (5)

• Health-related quality of life [Time frame: 8 weeks]
• Clinical complete response [Time frame: 8 weeks]
• The rate of conversion to resectable status [Time frame: 8 weeks]
• Pathological complete response [Time frame: 8 weeks]
• Overall survival [Time frame: 3 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years;
• Colorectal cancer confirmed by CT/MRI and colonoscopic biopsy；
• Patients unfit for surgery due to poor general condition or tumor extent and location;
• Patients who have not received prior chemotherapy or those who have undergone prior chemotherapy but remain chemosensitive.
• Adequate haematological, heart, liver and renal functions are required, with the following specific criteria: white blood cell count≥4000/mL, neutrophils≥1500/mm³, platelets≥100×10⁹/L, haemoglobin≥10.0 g/L, total bilirubin 2.0 mg/dL, aspartate aminotransferase 100 IU/L, alanine aminotransferase 100 IU/L, serum creatinine 1.5 mg/dL or creatinine clearance rate≥60 mL/min/body, and urine protein/creatinine<1.
• Patients have to have an expected life expectancy of ≥3months.
• All the subjects in this study are required to sign an informed consent form.

Exclusion criteria

• Patients with other primary malignant tumors;
• Patients with gastrointestinal perforation;
• Patients are allergic to the antitumor agents;
• Women who are pregnant, breastfeeding, or planning to become pregnant;
• Patients who receive other antitumor therapies concurrently, such as chemotherapy, targeted therapy, or radiotherapy;
• Patients with MSI-H/dMMR CRC；
• Patients for whom participation in the study is deemed to be inappropriate by the doctor in charge and/or the investigator for any other reasons.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Guang'anmen Hospital, China Academy of Chinese Medical Sciences — Xicheng

Identifiers

NCT: NCT07333053 · 2025-268-KY

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗