Second-line Standard Treatment Sequential TAS-102 and Bevacizumab Combined With Local Treatment in Advanced Colorectal Cancer

This study is a randomized, controlled, open-label, phase II clinical study. This study is designed to evaluate the efficacy and safety of second-line standard treatment sequential TAS-102 and bevacizumab combined with local treatment versus continuous treatment of standard second-line therapy in advanced colorectal cancer.

In this study, 119 metastatic colorectal cancer patients who reach CR/PR/SD after 3 months second-line treatment will be randomized to receive sequential TAS-102 +bevacizumab combined with local treatment or continuous treatment of previous second-line therapy. The primary endpoint is investigator-assessed time to treatment failure (TTF). Secondary endpoints include ORR, DCR, PFS, OS, safety and patient reported outcomes.

Inclusion criteria

• Unresectable colorectal adenocarcinoma confirmed by histopathology or cytology;
• Patients who have failed first-line standard therapy and are intended to receive second-line standard therapy;
• At least one measurable lesion according to RECIST 1.1 criteria;
• ECOG Performance Status 0-1;
• Estimated life expectancy ≥3months;
• Adequate major organ function;
• Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance.

Exclusion criteria

• Allergy to the investigational drug and/or its excipients;
• Pregnant or lactating women;
• Prior treatment with TAS-102;
• Any CTCAE grade 2 or above toxicity caused by previous treatment that has not yet subsided (excluding alopecia, skin pigmentation, and chemotherapy-induced neurotoxicity);
• Known inherited or acquired bleeding (e.g., coagulopathy) or thrombophilia, as in patients with hemophilia; Current or recent (within 10 days before initiation of study treatment) use of a full-dose oral or injectable anticoagulant or thrombolytic agent for therapeutic purposes (prophylactic use of low-dose aspirin and low-molecular-weight heparin is allowed);
• Serious illness, including but not limited to the following:

• Patients with other malignant tumors within 5 years before enrollment, except basal cell carcinoma of the skin or carcinoma in situ of the cervix;
• Known brain and/or leptomeningeal metastases;
• Active infection or fever of unknown origin > 38.5 ° C ;
• Poorly controlled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg) with a previous history of hypertensive crisis or hypertensive encephalopathy;
• Known inherited or acquired bleeding (e.g., coagulopathy)
• Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the initiation of study treatment;
• Severe, unhealed or dehiscence wounds and active ulcers or untreated fractures;
• Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (NYHA Class III or IV) within the last 12 months;
• Acute or subacute intestinal obstruction, or chronic inflammatory bowel disease;
• There are serious psychological or psychiatric abnormalities that affect the compliance of patients to participate in this clinical study.
• Has undergone major surgical treatment (excluding diagnosis) within 4 weeks before the start of the study or is expected to undergo major surgical treatment during the study period;
• Inability to swallow pills, presence of malabsorption syndrome or any condition affecting gastrointestinal absorption;
• The investigator assessed that it is not appropriate to participate in the study.