fruquintinib plus capecitabine versus bevacizumab plus capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer

Conditions: Colorectal Cancer

Summary: this is an open-label, multicenter, randomized phase 2 study evaluating the efficacy and safety of fruquintinib plus capecitabine versus bevacizumab plus capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer. patients who have already achieved disease control (including cr/pr and sd), without discontinuation for toxicity, and are progression free after 4-6 months of standard first-line induction treatment will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive fruquintinib + capecitabine (arm a) or bevacizumab + capecitabine (arm b). the study contains a safety lead-in phase in which the safety and tolerability of fruquintinib + capecitabine will be assessed prior to the phase 2 portion of the study. all patients from arm a and arm b will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal (whichever occurs earlier).


Eligibility criteria:
inclusion criteria: 1. 18-75 years old (including 18 and 75) at the time of signing the informed consent; 2. patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage iv); 3. patients who have achieved disease control (including cr/pr and sd) after 4-6 months of first-line standard chemotherapy (folfox, folfiri, xelox ± targeted therapy) and are progression free at the start of maintenance therapy; 4. at least one measurable metastatic lesion(s) as defined by recist version 1.1; 5. ecog performance status of 0-1; 6. body weight ≥40kg; 7. lvef≥50%; 8. life expectancy≥3 months; 9. adequate organ and bone marrow functions: neutrophils \>1.5×109/l, platelets \>100×109/l, and hemoglobin \>9 g/dl; total bilirubin \<1.5×upper limit of normal (uln); aspartate aminotransferase (ast)/serum glutamic-oxaloacetic transaminase (sgot) and/or alanine aminotransferase (alt)/serum glutamic-pyruvic transaminase (sgpt) \<2.5×uln (\<5×uln in case of liver metastases); creatinine clearance (calculated according to cockcroft and gault) ≥50 ml/min; urinary protein / creatinine ratio \< 1 (or urine analysis \< 1 + or 24-hour urinary protein \< 1g / 24 h); 10. able to take oral medication; 11. women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration; 12. 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; 3. those who have been proved to be allergic to fruquintinib and / or its excipients; 4. blood transfusion was performed within 1 week before randomization; 5. non-controlled hypertension after monotherapy, that is, systolic blood pressure \> 140mmhg or diastolic blood pressure \> 90mmhg; 6. intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure; 7. clinically significant electrolyte abnormality; 8. proteinuria ≥ 2+ (1.0g/24hr); 9. previous treatment with vegfr inhibition; 10. evidence of cns metastasis; 11. severe intolerance to capecitabine or 5-fu; 12. disability of serious uncontrolled intercurrence infection; 13. uncontrolled hemorrhage in gi; 14. have evidence or a history of bleeding tendency within two months of the enrollment; 15. abdominal fistula or gastrointestinal perforation occurred within 6 months before the first treatment, unless repaired by surgery; 16. within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including stroke and transient ischemic attack) , etc.; 17. within 6 months before the first recruitment occurs acute myocardial infarction, acute coronary syndrome or cabg; 18. incomplete healing of skin trauma, surgical site, wound site or severe mucosal ulcer. bone fracture or wounds that was not cured for a long time; 19. aptt and /or pt \>1.5×uln; 20. clinically detectable secondary primary malignancies at the time of enrollment, or had other malignancies in the past 5 years (excluding fully treated basal cell carcinoma of the skin or carcinoma in situ of the cervix); 21. patients who are not suitable for the study judged by the researchers.

Keywords: colorectal cancer fruquintinib maintenance