A Phase II Study on Dose Optimization of Fruquintinib in Elderly mCRC Patients Refractory to Standard Treatment（DOFEMCRC）

Inclusion Criteria:

1. 65 years and older;
2. Histologically or cytologically confirmed unresectable metastatic colorectal cancer refractory to or unfit for standard therapies;
3. ECOG PS 0-1;
4. At least 4 weeks after the last anti-tumor therapy (chemotherapy, radiotherapy, biotherapy or hormone therapy) and more than 3 months after operation treatment before enrollment;
5. Life expectancy ≥ 3 months;
6. Cooperative in observation of adverse events and curative effect;
7. No other anti-tumor concomitant treatment (including steroid drugs);
8. Adequate organ and bone marrow functions;
9. At least one measurable lesion(s);
10. Signed the written informed consent and completed the geriatric questionnaire (G8 screening form) at the time of enrollment.

Exclusion Criteria:

1. Active upper gastrointestinal ulcer, obvious vomiting, chronic diarrhea, intestinal obstruction, absorption disorder, etc which may affect drug absorption, distribution, metabolism, or clearance;
2. Evidence of central nervous system metastasis;
3. One of the following complications: uncontrolled hypertension, coronary artery disease, arrhythmia and heart failure;
4. Abuse of alcohol or drugs;
5. Less than 4 weeks from the last clinical trial;
6. Previous treatment with VEGFR inhibitors;
7. Severe uncontrolled disability with concurrent infection;
8. Proteinuria ≥ 2 + (1.0g / 24hr);
9. Uncontrollable gastrointestinal bleeding;
10. Arterial / venous thromboembolic events such as cerebrovascular accident (including transient ischemic attack) occurred within 12 months before the first dose;
11. Acute myocardial infarction, acute coronary syndrome or coronary artery bypass grafting occurred within 6 months before the first dose;
12. Fracture or wound that has not been cured for a long time;
13. Coagulation dysfunction, bleeding tendency or receiving anticoagulation treatment;
14. Congenital or acquired immune deficiency (such as HIV infection), or active hepatitis (HBV DNA ≥ 103copies / ml after regular antiviral therapy);
15. Patients who are not suitable for the study judged by the researchers.