A Single-arm, Open-label Clinical Study of Irinotecan Liposome Combined With Capecitabine, Bevacizumab and Camrelizumab as Second-line or Higher Treatment for Patients With Metastatic Colorectal Cancer
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer (CRC)
Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine

Version 1.1, October 10,2025
Essential
Page 1
s
Research Title
A single-arm, open-label clinical study of irinotecan liposome combined with capecitabine,
bevacizumab, and camrelizumab as second-line or later treatment for patients with metastatic rectal
carcinoma
Version and Date
V1.1
October 10,2025
Principal Investigator
Li Dezhi
Clinical TRIAL LEADERS
Unit
The Fourth Affiliated Hospital of Zhejiang University School of Medicine
Research type
Prospective, single-arm clinical study
Indication
Metastatic rectal carcinoma
Planning study period
3 years
Subject investigated
Diagnosed as metastatic rectal carcinoma by histology or cytology
Purpose of research
Primary research objectives:
Progression-free survival (PFS) assessed by the investiga-
tors
Secondary objectives:
1)
The objective response rate (ORR), duration of response (DoR), disease
control rate (DCR), and overall survival (OS) assessed by the investigators;
2)
Evaluate the safety of irinotecan liposome combined with capecitabine,
bevacizumab, and camrelizumab for second-line and above treatment of
metastatic colorectal carcinoma patients;
Planned enrollment
68 Example
Research design
Prospective, single-arm study

Version 1.1, October 10,2025
Enrollment Criteri
Page 2
a
1.
Patients with a pathological diagn-
osis of rectal carcinoma;
2.
They have received systematic
treatment on the front line;
3.
18-75
years
of
age,
male
and
female;
4.
There must be at least one measurable lesion as the target lesion (according to
RECIST v1.1 criteria);
5.
ECOG：0～1；
6.
expected survival ≥3 mo-
nths;
7.
Women of childbearing age must have a negative blood pregnancy test within 3
days prior to randomization and be willing to use appropriate contraceptive
methods during the trial and for 6 months after treatment. For men, consent
must be obtained to use appropriate contraceptive methods during the study and
for 3 months after treatment.
8.
All participants voluntarily enrolled in this study and
signed the informed consent form.
Exclusion criteria
1.
Patients with both RAS and BRAF wild-type mutations and left-sided
primary colorectal tumors who have not received cetuximab in first-line
therapy
2.
patients with advanced rectal carcinoma who
have MSI-H or dMMR
3.
For patients with a history of other malignant diseases in the past 5 years,
cured skin cancer and in situ cancer of cervix are excluded.
4.
For patients with uncontrolled epilepsy, disorder central nervous system, or a
history of mental disorders, the investigator may determine that their clinical
severity could hinder the signing of an informed consent form or affect the
patient's adherence to oral medication.
5.
Clinically severe (i.e., active) heart disease, such as symptomatic coronary
artery disease, congestive cardiac failure of NYHA class II or worse, or
severe arrhythmias requiring pharmacological intervention (see Appendix
12), or a history of infarct myocardial within the past 12 months.
6.
Organ transplant recipients requiring
immunosuppression therapy
7.
Severe, uncontrolled recurrent infections, or other severe, uncontrolled
comorbidities
8.
The baseline blood routine and biochemical indicators of the subjects did not
meet the following criteria: hemoglobin ≥90g/L; absolute neutrophil count
(ANC) ≥1.5 × 109/L; platelet count ≥100 × 109/L; ALT, AST ≤2.5 times
the upper limit of normal; ALP ≤2.5 times the upper limit of normal; serum
total bilirubin <1.5 times the upper limit of normal; serum creatinine <1
times the upper limit of normal; serum albumin ≥30g/L.
9.
Known to have a deficiency in dihydropyridine
dehydrogenase (DPD)
10. Allergy to any of the investigational drug components (e.g., irinotecan,
irinotecan liposome, capecitabine, bevacizumab, or camrelizumab)
11. pregnant or lactat-
ing women

Version 1.1, October 10,2025
12. received any of the follow
Page 3
-
ing treatments:

Concomitant medications within the first 2 weeks of randomization contained strong
inhibitors/strong inducers of CYP3A4 or CYP2C8, or strong inhibitors of UGT1A1.

Use of immunosuppressants or systemic hormone therapy for the purpose of
immunosuppression within the first 2 weeks (dose>10mg/day of prednisone or
other equivalent therapeutic hormones);

received radiotherapy within the first 2
weeks of randomization;

Surgery
(e.g.
thoracotomy,
laparotomy)
in
the
first
4
weeks
of
randomization;

Received any other investigational drug in the previous 4 weeks, except for
observational (non-interventional) clinical studies or intervention clinical study
follow-up.
13. Coagulation dysfunction, having haemorrhagic diathesis or undergoing thrombolytic
or anticoagulant therapy. The prophylactic use of low-dose aspirin (≤100mg/day)
and
low-molecular-weight
heparin
(enoxaparin
40mg/day
and
other
low-
molecular-weight heparins at equivalent doses) is permitted.
Administration method

Iritinib liposome: 60 mg/m², administered via intravenous
infusion, with the infusion completed within 90 minutes (±5
minutes). Administration is scheduled on day 1, once every 3 weeks.

Capecitabine: 800 mg/m2, orally, twice daily, for days 1
to 14, repeated every 3 weeks.

Bevacizumab: 7.5 mg/kg, intravenous infusion, on day 1,
administered every 3 weeks;

Crelizumab: 200 mg, intravenous infusion, on day 1,
administered every 3 weeks
Therapeutic evaluation
RECIST1.1 was used.
Safety evaluation
NCI CTCAE 5.0 was used.
Evaluating indicator
Life signs, blood, urine, stool routine tests, blood biochemistry, electrocardi-
ogram, echocardiography, observation of chemotherapy toxicity reactions, etc.
Subgroup analysis
PD-1 immunological detection stratification
Sample size calculation
The progression-free survival (PFS, Recist v1.1) of patients with metastatic
rectal carcinoma treated with irinotecan liposome combined with capecitabine,
bevacizumab, and camrelizumab in second-line or later therapy was improved
from 5.7 months in previous studies to 8.3 months, α=0.05.

Version 1.1, October 10,2025
With a power of 0.80,62 samples are required, and considering a 10% attrition rate, 68 participants are planned to be enrolled
Page 4
.
This study is an exploratory study aimed at preliminarily evaluating the
progression-free survival (PFS, Recist v1.1) of patients with metastatic rectal
carcinoma treated with irinotecan liposome combined with capecitabine, bevaci-
zumab, and camrelizumab as second-line or later therapy, without formal statistical
assumptions. Statistical tests were not powered (Power) calculated or adjusted for
multiplicity. All P-values for statistical tests were two-sided, with nominal P
values.
Research progress
The first subject is expected to be enrolled in November 2025.
The estimated enrollment date for the last subject is November 2027.
The study is expected to conclude in November 2028.