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 criteria and do not meet the exclusion criteria for receiving third-line or later-line therapy will be 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 or unacceptable toxicity during treatment or within three months following completion of therapy.

   (Note: a. each line of therapy should include at least one or more chemotherapy agents administered for at least one cycle; b. adjuvant/neoadjuvant therapy is allowed. If relapse or metastasis occurs during or within six months after completion of adjuvant/neoadjuvant therapy, it is considered a failure of first-line chemotherapy for progressive disease. c. For patients with RAS/RAF wild-type tumors, the use of an EGFR inhibitor is not required.)
3. At least one measurable lesion, with the longest diameter ≥10 mm on spiral CT or ≥20 mm 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 period prior 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, and creatinine 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 to participate 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 digestive ulcers and fecal occult blood (++) and those with histories of black stools or hematemesis within three months.
4. Receiving systemic antitumor therapy, including chemotherapy, signal transduction inhibitors, or immune therapies, within three weeks prior to screening.
5. Patients with uncontrolled hypertension (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg) despite antihypertensive medication, grade I or higher coronary heart disease, grade I or higher arrhythmia (including QTc interval prolongation with ≥450 ms for men and ≥470 ms for women), or grade I or higher heart failure.
6. Patients with a history of thrombotic or embolic events requiring treatment within the preceding 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 adequate contraception.
13. Multiple factors affecting oral drug administration (dysphagia, chronic diarrhea, and bowel obstruction).
14. Patients who have been treated with small molecule tyrosine kinase inhibitors containing 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 affect their completion of the study.