Hepatic Arterial Infusion Pump (HAIP) Combined With Fuquinitinib as Late-line Treatment in Patients With Colorectal Cancer Liver Metastases（CRLM）: A Phase 2 Single-Arm Clinical Trial
Phase: PHASE2
Conditions: Colorectal Neoplasms
Sponsor: Meng Qiu

Version number：1.0
Date of version：January 1, 2023
Fuquinitinib combined with FOLFOXIRI-HAIP is used as a Later-line Treatment for
Patients with advanced Colorectal Cancer Liver Metastasis.
Project Leader (signature)：Meng Qiu
Telephone number：+8618980601776
1. Background
About 30-50% of patients with colorectal cancer have liver metastases at the time of
diagnosis. Surgical resection is the standard radical treatment for patients with resectable
colorectal cancer liver metastases, but only about 20% of patients with colorectal cancer liver
metastases can achieve long-term survival after surgical treatment, and more than 70% of patients
with colorectal cancer liver metastases are initially unresectable or relapse after liver resection.
There is still a lack of effective treatment for unresectable colorectal liver metastases. Previous
studies have shown that three-drug regimen FOLFOXIRI (oxaliplatin, fluorouracil, irinotecan and
leucovorin) is superior to two-drug FOLFOX or FOLFIRI in the treatment of advanced colorectal
cancer, and can be used as a first-line treatment for some patients. However, most patients with
metastatic CRC have disease progression despite receipt of first - or second-line systemic therapy.
Fuquinitinib, an oral small molecule vascular endothelial growth factor receptor (VEGFR)
inhibitor developed in China, has a limited effect on improving overall survival in patients with
advanced metastatic colorectal cancer. Transarterial embolization (TACE) and hepatic arterial
infusion chemotherapy (HAIC) are two interventional methods for the treatment of liver
metastases from colorectal cancer. Hepatic arterial infusion pump chemotherapy (HAIP) is based
on HAIC. The arterial port can be placed in the femoral artery for a long time, and the drug can be
given regularly or at any time according to the need. Therefore, the aim of this study is to explore
the survival benefits and prognostic factors of fuquinitinib combined with FOLFOXIRI-HAIP in
the third-line or beyond treatment of advanced colorectal cancer patients with liver metastasis.
2. Aim and Content of the Study
2.1 Aim of the study
To prospectively collect and analyze the efficacy and safety of fuquinitinib combined with
FOLFOXIRI-HAIP regimen in the late-line treatment of patients with metastatic colorectal cancer.
2.2 Content of the study

Inclusion criteria:
a. Men and women over 18 years old;
b. Colorectal cancer confirmed by pathology or cytology, with liver metastasis only, or liver as the
main metastatic tumor burden site, and unable to undergo surgical resection or unwilling to
undergo surgical resection;
c. Patients who had received oxaliplatin, fluorouracil, or irinotecan chemotherapy with or without
EGFR monoclonal antibody or VEGFR monoclonal antibody;
d. The main organ function (liver, kidney, heart, lung) was normal and Eastern Cooperative
Oncology Group Performance Status (ECOG PS) score of 0 to 2.
E. All participants were willing to participate in this clinical study, and were required to sign the
corresponding informed consent. They had good compliance during the treatment and follow-up
process, and were willing to cooperate with the relevant research process.


Exclusion Criteria:
a. Prior treatment with TACE, HAIC or fuquinitinib；
b. Combined with primary malignant tumors of other systems except colorectal cancer;
c. Allergy to study medication;
d. Major organ functions (liver, kidney, heart, lung) were severely abnormal.
2.3 Sample size: 24
This single-center, single-arm, a phase 2 clinical trial performed at the West China Hospital.
Sample size calculation used a two-stage Simon’s optimal design with nominal alpha and beta
values of 5% and 20%, respectively. The null hypothesis stated that ORR would be ≤10%, versus
an alternative hypothesis of ORR ≥35%. Accounting for a 10% dropout rate, at least 24 patients
were required for this study. This study included 8 patients in Stage 1and 39 patients in Stage 2.
Stage 2 enrollment was only initiated after ≥1 partial response had been observed in 8 treated
patients. The study adhered to the guidelines outlined in the Declaration of Helsinki and has been
approved by the Ethics Committee of West China Hospital, Sichuan University. All patients
provided written informed consent for participation in the study.
2.4 Outcome Measures
Eligible
patients
were
enrolled
from
January
2023
to
receive
furoquininib
plus
FOLFOXIRI-HAIP. The baseline data (including age, gender, some blood indicators before
treatment, primary tumor location, tumor stage, pathological differentiation type, gene mutation
status, number of previous treatment lines, size and number of liver metastases), adverse reactions,
overall survival (OS) and progression-free survival (PFS) were collected and summarized.
The primary endpoint of the study was objective response rate (ORR). The secondary
endpoints included overall progression-free survival (PFS), overall survival (OS), liver-specific
PFS and safety evaluation. ORR was defined as the proportion of patients with the best overall
response of complete response (CR) and partial response (PR). OS was defined as the duration
from the initiation of treatment to loss to follow-up or death. PFS was defined as the duration from
the start of treatment to disease progression or death.
3. Statistical analysis
Continuous variables were expressed as means ± standard deviations (SD), along with the
minimum and maximum values. For non-normally distributed data, the IQR was used. Categorical
variables were presented as frequencies and percentages. The Kaplan-Meier method was used to
analyze OS and PFS in the overall population with estimated medians and 95% CIs presented.
Survival curves were performed using R software version 4.2.2 (http://www.Rproject.org).
4. Ethical principles and requirements of clinical research
Clinical research will follow the Declaration of Helsinki of the World Medical Assembly and
the Ethical Review Measures for Biomedical Research involving Human Subjects of the National
Health and Family Planning Commission of the People's Republic of China and other relevant
regulations, including the principles and requirements of informed consent, privacy protection,
research free of charge and compensation, risk control, protection of special subjects and
compensation for research-related damages. The clinical study was carried out after approval of
the trial protocol by the ethical review board prior to the initiation of the study. Before each
subject is enrolled in the study, the investigator is responsible for providing the subject or/and
his/her legal representative with a complete and comprehensive introduction of the purpose,
procedures and possible risks of the study, and signing a written informed consent form, so that

the subject knows that their participation in the clinical study is completely voluntary. They may
refuse to participate or withdraw from the study at any stage without discrimination or retaliation,
and their medical treatment and rights and interests will not be affected. Informed consent should
be retained as a clinical research document for future reference to effectively protect the personal
privacy and data confidentiality of subjects.
5. References
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