Regorafenib Combined With TAS-102 Versus Regorafenib Monotherapy in Third or Later Line Therapy of mCRC

A total of 101 patients with metastatic colorectal cancer who meet the inclusion criteriaand do not meet the exclusion criteria for receiving third-line or later-line therapy willbe randomly assigned to receive corresponding treatment in a 1:1 ratio. Inclusion Criteria: The subjects must meet all of the following criteria to be eligible for this study:

1. Patients with histologically confirmed recurrent/metastatic colorectal adenocarcinoma.
2. Patients who have failed at least one prior standard first- or second-line therapy,including fluoropyrimidine-based therapy, oxaliplatin, irinotecan, and bevacizumab.Treatment failure is defined as either radiographic evidence of disease progression orunacceptable toxicity during treatment or within three months following completion oftherapy. (Note: a. each line of therapy should include at least one or more chemotherapy agentsadministered for at least one cycle; b. adjuvant/neoadjuvant therapy is allowed. Ifrelapse or metastasis occurs during or within six months after completion ofadjuvant/neoadjuvant therapy, it is considered a failure of first-line chemotherapyfor progressive disease. c. For patients with RAS/RAF wild-type tumors, the use of anEGFR inhibitor is not required.)
3. At least one measurable lesion, with the longest diameter ≥10 mm on spiral CT or ≥20mm on conventional CT (RECIST 1.1 criteria).
4. ECOG performance status of 0-2.
5. Life expectancy of ≥12 weeks.
6. Adequate bone marrow, hepatic, and renal function measured within the screening periodprior to randomization: absolute neutrophil count (ANC) ≥1.5 × 109 /L, hemoglobin ≥ 8.0 g/dL, platelet count ≥ 75 × 109 /L, total bilirubin <1.5 × ULN, ALT and AST <2.5 ×ULN (≤5 × ULN for patients with liver involvement), serum creatinine ≤1.5 × ULN, andcreatinine clearance ≥50 mL/min.
7. Women of childbearing potential must use effective contraception.
8. Voluntarily participating in this study, signing the informed consent form,understanding the purpose of the study and the necessary procedures, and willing toparticipate in this study.

Exclusion Criteria: Patients who meet any of the following criteria will be excluded from the study:

1. Proteinuria ≥2+ on dipstick or 24-hour urinary protein ≥1.0 g/24 h.
2. Abnormal coagulation function (PT>16s, APTT>43s, TT>21s, Fbg<2g/L), bleeding tendency,or receiving thrombolysis or anticoagulation therapy.
3. Patients at risk of gastrointestinal bleeding, including those with active digestiveulcers and fecal occult blood (++) and those with histories of black stools orhematemesis within three months.
4. Receiving systemic antitumor therapy, including chemotherapy, signal transductioninhibitors, or immune therapies, within three weeks prior to screening.
5. Patients with uncontrolled hypertension (systolic blood pressure >140 mmHg, diastolicblood pressure >90 mmHg) despite antihypertensive medication, grade I or highercoronary heart disease, grade I or higher arrhythmia (including QTc intervalprolongation with ≥450 ms for men and ≥470 ms for women), or grade I or higher heartfailure.
6. Patients with a history of thrombotic or embolic events requiring treatment within thepreceding six months.
7. Patients who have received radiation therapy targeting the selected target lesion.
8. Symptomatic brain or meningeal metastasis.
9. Uncontrolled pleural or peritoneal effusion.
10. Receiving kidney dialysis.
11. Serious or uncontrolled infection.
12. Pregnant or lactating women or women of childbearing potential without adequatecontraception.
13. Multiple factors affecting oral drug administration (dysphagia, chronic diarrhea, andbowel obstruction).
14. Patients who have been treated with small molecule tyrosine kinase inhibitorscontaining VEGFR (such as apatinib, fruquintinib, anlotinib, and lenvatinib).
15. Patients who have been treated with TAS-102.
16. Participation in another clinical study within four weeks prior to screening.
17. Patients with comorbidities that could seriously endanger patients' safety or affecttheir completion of the study.