A Prospective Multi-centered Randomized Controlled Trial on Fruquintinib in Combination With HAIC in the Treatment of Liver Metastatic Colorectal Cancer After Failure of Second-line Systematic Therapy

  • End date
    Dec 31, 2024
  • participants needed
  • sponsor
    Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Updated on 4 October 2022


The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.


Among Chinese colorectal cancer patients, 43.8% had metastasis at the time of diagnosis, of which liver metastasis accounted for 51.5%. In addition, it was reported that 10%-25% of patients developed liver metastasis after radical resection of colorectal cancer, and more than two-thirds of colorectal patients eventually developed liver metastasis. Colorectal liver metastasis was reported to be the most important cause of death in colorectal cancer patients.The median survival time of untreated liver metastases was only 6.9 months, and the 5-year survival rate of unresectable patients was less than 5%, and for unresectable colorectal liver metastasis, the median survival time could reach 30.9 months after comprehensive treatment.

Fruquintinib, a VEGFR 1/2/3 inhibitor, is one of the standard 3rd-line therapy for colorectal cancer, which has already been approved and marketed in China. In phase III FRESCO study, liver metastases subgroup showed that the median OS of fruquintinib group was 8.61 months, which was 2.63 months longer than that of control group, reducing death risk by 41%, with statistically significant P value.

Patients with large tumor burden mainly caused by liver metastasis and with insignificant or refractory response to drug therapy, or patients who cannot tolerate systemic therapy, can be combined with transcatheter arterial chemoembolization (HAI) or transcatheter arterial chemoembolization (TACE) at appropriate time, which helps to prolong the progression-free time and overall survival.

The current study is to investigate the safety and efficacy of fruquintinib combined with HAIC in patients with advanced colorectal liver metastases who have failed second-line systemic standard treatment, in order to provide more survival opportunities for the second progression of advanced colorectal liver metastases.

Condition Colorectal Cancer
Treatment Fruquintinib, HAIC
Clinical Study IdentifierNCT05511051
SponsorCancer Institute and Hospital, Chinese Academy of Medical Sciences
Last Modified on4 October 2022


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Inclusion Criteria

Fully understand the study and voluntarily sign the informed consent form
Age ≥ 18 years
Patients with unresectable colorectal liver metastases who have failed standard second-line systemic therapy, who have not previously received HAIC therapy, and have not received third-line standard targeted agents (regorafenib or fruquintinib or trifluridine tipiracil (TAS-102)
Definition of liver metastases: at least 1 measurable liver metastasis lesion (based on RECIST 1.1); if the liver metastases are single, the tumor is > 5 cm; if multiple tumors, it needs to be greater than or equal to 4, of which at least 1 exceeds 3 cm
PFS > 4 months from last dose of oxaliplatin with FOLFOX regimen
Child-Pugh classification of liver function: A
ECOG performance status 0-1, and no deterioration within 7 days
BMI ≥ 18
Expected survival ≥ 3 months
Vital organs function in accordance with the following requirements (any blood components and cell growth factors are not allowed within 14 days before enrollment)
Absolute neutrophil count ≥ 1.5 × 109/L and white blood cells ≥ 4.0 × 109/L
Platelets ≥ 100 × 109/L
Hemoglobin ≥ 90 g/L
Total bilirubin TBIL ≤ 1.5 times ULN
ALT and AST ≤ 5 times ULN
Urea nitrogen/urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN (and creatinine clearance (CCr) ≥ 50 mL/min)
Left ventricular ejection fraction (LVEF) ≥ 50%
Fridericia-corrected QT interval (QTcF) < 470 milliseconds
INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN
women of childbearing age need to take effective contraceptive measures
good compliance and cooperation with follow-up

Exclusion Criteria

Unable to comply with the study protocol or study procedures
Pregnant or breastfeeding women
Any factor affecting oral administration
Evidence of central nervous system metastases
Concurrent with any of the following: uncontrolled hypertension, coronary artery disease, arrhythmia, and heart failure
Alcohol or drug abuse within 4 weeks after the last clinical trial
Previous VEGFR inhibition therapy
Uncontrolled severe concurrent infection resulting in disability
Proteinuria ≥ 2 + (1.0 g/24 h)
Evidence or history of bleeding tendency within 2 months prior to enrollment, regardless of seriousness
Arterial/venous thromboembolic events, such as cerebrovascular accidents (including transient ischemic attack), within 12 months before the first treatment
Acute myocardial infarction, acute coronary syndrome or CABG within 6 months before the first treatment
Fractures or wounds that have not been cured for a long time
coagulopathy, bleeding tendency or receiving anticoagulant therapy
Inactivated vaccines within 4 weeks prior to enrollment or possible during the study
Patients with other malignant tumors within 5 years before enrollment, except for basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ
Active autoimmune diseases or history of autoimmune diseases within 4 weeks before enrollment
Previous allogeneic bone marrow transplantation or organ transplantation
Subjects who are allergic to the study drug or any of its adjuvant preparations
Electrolyte abnormalities judged clinically significant by the investigator
Known human immunodeficiency virus (HIV) infection. Known history of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must have excluded active HBV infection, ie, positive HBV DNA (> 1 × 104 copies/mL or > 2000 IU/mL); known hepatitis C virus (HCV) infection and positive HCV RNA (> 1 × 103 copies/mL)
Unresolved toxicities above CTCAE v5.0 grade 1 due to any prior anticancer therapy, excluding alopecia, lymphopenia, and oxaliplatin-induced neurotoxicity ≤ grade 2
Received blood transfusion therapy, blood products and hematopoietic factors, such as albumin and granulocyte colony-stimulating factor (G-CSF), within 28 days before enrollment
with brain metastases, or with severe malignant pleural effusion and ascites
Any other diseases, clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the investigator 's judgment, there is reason to suspect that the patient has a disease or condition that is not suitable for the use of the study drug (such as having seizures and requiring treatment), or will affect the interpretation of the study results, or put the patient at high risk
Patients who are considered unsuitable for inclusion in this study by the investigator
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