fruquintinib combined with tas-102 in the treatment of patients with advanced metastatic crc

Conditions: Metastatic Colorectal Cancer

Summary: this phase ii study aims to explore the efficacy and safety of fruquintinib combined with tas-102 in the third-line treatment of patients with advanced metastatic colorectal cancer.

this is a prospective, single center, one-arm phase ii study. a total of 54 advanced mcrc patients refractory to standard therapies will be enrolled and administered with fruquintinib (4mg/d, qd po, d1-21, q4w) combined with tas-102 (70mg/m2/d, bid po, d1-5, 8-12, q4w) until intolerable toxicity, disease progression or death. primary endpoint of this study is pfs and secondary endpoints are os, orr, dcr and safety.

Eligibility criteria:
inclusion criteria: 1. ≥ 18 and ≤ 75 years of age; 2. histological or cytological confirmed advanced metastatic colorectal cancer; 3. refractory to at least second line standard treatment containing fluorouracil, oxaliplatin and irinotecan; 4. at least one measurable lesion (larger than 10 mm in diameter by spiral ct scan or 20mm by conventional ct scan); 5. ecog performance status of 0-1; 6. life expectancy ≥ 12 weeks; 7. no previous treatment with vascular endothelial growth factor receptor (vegfr) inhibitor (tki); 8. signed and dated informed consent; 9. adequate hepatic, renal, heart, and hematologic functions; 10. willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure. exclusion criteria: 1. pregnant or lactating women; 2. any factors that influence the usage of oral administration or any disease or condition that affects drug absorption; 3. previous treatment with tas-102; 4. participated in clinical trials of other drugs within four weeks before enrollment; 5. received other systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, signal transduction inhibitors, hormone therapy and immunotherapy; 6. international normalized ratio (inr) \> 1.5 or partially activated prothrombin time (aptt) \> 1.5 × uln; 7. clinically significant electrolyte abnormalities; 8. subjected with hypertension that cannot be controlled by drugs, which is specified as: systolic blood pressure ≥ 140 mmhg and / or diastolic blood pressure ≥ 90 mmhg; 9. unrelieved toxic reactions higher than ctcae v5.0 grade 1 caused by any previous anti-cancer treatment; 10. incomplete healing of skin wound, surgical site, traumatic site, severe mucosal ulcer or fracture; 11. conditions that may cause gastrointestinal bleeding and perforation determined by the researcher; 12. history of arterial thrombosis or deep venous thrombosis within 6 months before enrollment; 13. stroke and / or transient cerebral ischemia occurred within 12 months before enrollment; 14. cardiovascular diseases with significant clinical significance; 15. lvef\<50%; 16. congestive heart failure new york heart association (nyha) grade \> 2; 17. evidence of cns metastasis; 18. previous treatment with vegfr inhibition; 19. ventricular arrhythmias requiring drug treatment; 20. proteinuria ≥ 2+ (1.0g/24hr); 21. coagulation dysfunction, hemorrhagic tendency or receiving anticoagulant therapy; 22. other malignant tumors in the past 5 years, except skin basal cell or squamous cell carcinoma after radical surgery, or cervical carcinoma in situ; 23. active infection that is not controlled clinically, such as acute pneumonia, active hepatitis b or hepatitis c; 24. by judgment of the investigator, there are concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study.