| Eligibility |
Inclusion Criteria:
1. Subjects voluntarily enrolled in the study and signed an informed consent form, were
compliant and cooperated with follow-up visits;
2. Patients with metastatic colorectal adenocarcinoma confirmed by pathology or
histology;
3. Patients with second-line metastatic colorectal adenocarcinoma who have failed prior
standard first-line treatment (recurrence within 6 months of the end of adjuvant
chemotherapy is considered first-line treatment failure);
4. Tumor tissue testing at the primary or metastatic site allows enrollment in
second-line therapy regardless of whether the KRAS, NRAS, or BRAF genes are wild-type
or mutant, and regardless of microsatellite status as MSS/ pMMR or MSI-H/dMMR. For
MSI-H/dMMR patients, first-line treatment was similarly allowed for enrollment if
immunotherapy was used in the second line;
5. Age: 18-75 (inclusive of 18 and 75), male or female;
6. ECOG score: 0-1;
7. Expected survival = 3 months;
8. At least one measurable lesion (based on RECIST 1.1 criteria);
9. Patients must undergo UGT1A1 genetic testing;
10. Major organs and bone marrow function were essentially normal (no blood components or
cell growth factors had been used in the 14 days prior to enrollment):
1)Blood count: leukocytes = 3.5 x 109 /L, neutrophils = 1.5 x 109 /L, platelets = 100 x 109
/L, hemoglobin = 90 g/L; 2)International normalized ratio (INR) = 1.5 x upper limit of
normal (ULN) and activated partial thromboplastin time (APTT) = 1.5 x ULN; 3)Liver
function: total bilirubin = 1.5 x ULN; ALT/AST/ALP = 2.5 x ULN in the absence of liver
metastases; ALT/AST/ALP = 5 x ULN in the presence of liver metastases; 4)Renal function:
serum creatinine = 1.5 x ULN and creatinine clearance (CCr) = 60 mL/min (see Appendix);
5)Normal cardiac function with left ventricular ejection fraction (LVEF ) =50% by 2D
cardiac ultrasound; 11. Male or female patients of childbearing potential will voluntarily
use an effective method of contraception, e.g., double-barrier contraception, condoms, oral
or injectable contraceptives, intrauterine devices, etc., for the duration of the study and
for 6 months after the last study dose. All female patients will be considered of
childbearing potential unless the female patient is naturally menopausal, has undergone
artificial menopause or sterilization (e.g., hysterectomy, bilateral adnexectomy, or
radiation ovarian irradiation, etc.), unless the female patient has a serum or urinalysis
that shows no pregnancy within the 7 days prior to the study, and must be a non-lactating
patient.
Exclusion Criteria:
1. Patients who are allergic to furaquintinib, irinotecan, and capecitabine;
2. Received anti-angiogenic small molecule TKI class (regorafenib, apatinib, lenvatinib,
amlotinib, etc.) medications other than furoquinotinib prior to enrollment, etc;
3. Patients using furaquintinib and irinotecan prior to enrollment;
4. Those who have participated in a clinical trial of another antitumor drug within 4
weeks prior to enrollment or who are in the process of conducting another clinical
trial;
5. Other malignancy within the past 5 years, except basal or squamous cell carcinoma of
the skin after radical surgery, or carcinoma in situ of the cervix;
6. The patient has any current disease or condition that interferes with drug absorption
or the patient is unable to take furaquintinib orally;
7. Any surgical (except biopsy) or invasive treatment or manipulation within 4 weeks
prior to the start of enrollment and the surgical incision has not completely healed
(except for intravenous cannulation, puncture drainage, etc.);
8. There is pleural effusion, pericardial effusion, ascites, and it causes the patient to
cause respiratory syndrome (= CTC AE grade 2 dyspnea);
9. Clinically significant electrolyte abnormalities as judged by the investigator;
10. Patients with current hypertension uncontrolled by medications were defined as
patients who had hypertension and could not obtain good control with antihypertensive
medication (systolic blood pressure =150 mmHg and diastolic blood pressure 100 mmHg);
11. Urine routine suggests urinary protein =3+ and the amount of urinary protein >3.5g in
24 hours; and
12. Patients with current GI disease such as active gastric and duodenal ulcers,
ulcerative colitis, or active bleeding from unresected tumors, or other conditions
that may cause GI bleeding or perforation as determined by the investigator;
13. Patients with evidence or history of significant bleeding tendency within 3 months
prior to enrollment (bleeding >30 mL within 3 months, vomiting blood, black stool,
blood in stool), hemoptysis (>5 mL of fresh blood within 4 weeks), or a thromboembolic
event (including stroke events and/or transient ischemic attack) within 6 months;
14. Clinically significant cardiovascular disease including, but not limited to, acute
myocardial infarction, severe/unstable angina, or coronary artery bypass grafting
within 6 months prior to enrollment; new-onset angina pectoris in the 3 months prior
to enrollment; congestive heart failure New York Heart Association (NYHA)
classification >2; ventricular arrhythmias requiring pharmacologic therapy;
15. Active or uncontrolled serious infection (= CTCAE grade 2 infection);
16. Women who are pregnant (positive pregnancy test prior to administration) or are
breastfeeding;
17. Any other disease, clinically significant metabolic abnormality, physical examination
abnormality, or laboratory test abnormality that, in the investigator's judgment,
gives reason to suspect that the patient has a disease or condition for which the
investigational drug is inappropriate (e.g., seizures requiring treatment), or that
will interfere with the interpretation of the results of the study, or that puts the
patient at high risk;
18. Known human immunodeficiency virus (HIV) infection; known history of clinically
significant liver disease, including viral hepatitis [known hepatitis B virus (HBV)
carriers must exclude active HBV infection, i.e., HBV DNA positive (>1 × 104 copies/mL
or >2000 IU/ml); known hepatitis C virus infection (HCV) and HCV antibody positive, or
other hepatitis or cirrhosis;
19. In the judgment of the investigator, the patient has other factors that may affect the
results of the study or cause this study to be forced to be terminated midway, such as
alcoholism, drug abuse, other serious illnesses (including psychiatric illnesses) that
require comorbid treatment, serious laboratory test abnormalities, concomitant family
or societal factors that would affect the patient's safety;
20. Patients with brain metastases or/and carcinomatous meningitis;
21. Received radiotherapy within 4 weeks prior to enrollment and the lesion observed in
this study was in the radiotherapy target area; Comorbidities requiring prolonged
treatment with immunosuppressive drugs or systemic or topical corticosteroids at
immunosuppressive doses (>10 mg/day of prednisone or other active hormones).
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