neoadjuvant treatment of fruquintinib combined with concurrent chemoradiotherapy for larc

Conditions: Rectal Cancer

Summary: the study aims to evaluate the efficacy and safety of fruquintinib combined with mfolfox6 + synchronous radiotherapy as neoadjuvant therapy in middle and low locally advanced rectal cancer patients with no previous anti-tumor treatment.

the study aims to evaluate the efficacy and safety of fruquintinib combined with mfolfox6 + synchronous radiotherapy as neoadjuvant therapy in middle and low locally advanced rectal cancer patients with no previous anti-tumor treatment. approximately 40 patients will be enrolled and undergo combination neoadjuvant therapy, followed by tme and mfolfox6 adjuvant therapy, peri-operative treatment will last for 6 months. the primary endpoint is pcr.

Eligibility criteria:
inclusion criteria: * histologically confirmed rectal adenocarcinoma, classified as stage ii (t3-4n0) or stage iii (t1-4n1-2) by mri and ct; * middle and low rectal cancer with the lower pole of the tumor less than 12 cm from the anal margin; * the multidisciplinary cancer committee recommended neoadjuvant radiotherapy, chemotherapy and surgery; * ecog ps 0-1; * expected survival ≥ 2 years; * have not received any anti-tumor treatment; * have at least one measurable lesion; * sufficient organs and bone marrow functions; * women of childbearing age need to take effective contraceptive measures; exclusion criteria: * patients with surgical contraindication; * patients with familial adenomatous polyposis (fap), hereditary nonpolyposis colorectal cancer (hnpcc), active crohn's disease or active ulcerative colitis; * other malignant tumors found within 5 years before enrollment, except skin basal cell or squamous cell carcinoma, or cervical carcinoma in situ after radical surgery; * serious cardiovascular disease, including unstable angina pectoris or myocardial infarction, occurred within 6 months before enrollment; * international normalized ratio (inr)\>1.5 or partially activated prothrombin time (aptt)\>1.5 × uln； * investigators judged clinically significant electrolyte abnormalities; * hypertension that could not be controlled by drugs before enrollment, which was defined as: systolic blood pressure ≥ 140 mmhg and/or diastolic blood pressure ≥ 90 mmhg; * poorly controlled diabetes mellitus before enrollment (fasting glucose concentration ≥ ctcae level 2 after regular treatment); * active ulcer of stomach and duodenum, ulcerative colitis and other digestive tract diseases before enrollment, or other conditions that may cause gastrointestinal bleeding and perforation judged by the researcher; * serious active bleeding, hemoptysis (\>5 ml fresh blood within 4 weeks) or thromboembolism (including stroke and/or transient ischemic attack) occurred within 12 months before enrollment; * cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; congestive heart failure new york heart association (nyha) grade\>2; ventricular arrhythmias requiring medication; lvef\<50%; * active or uncontrollable serious infection (≥ ctcae v5.0 grade 2 infection); * known human immunodeficiency virus (hiv) infection. a known history of liver disease with clinical significance, including viral hepatitis \[people who are known to be carriers of hepatitis b virus (hbv) must exclude active hbv infection, that is, hbv dna positive (\>1 × 104 copies/ml or\>2000 iu/ml); known hepatitis c virus infection (hcv) and hcv rna positive (\>1 × 103 copies/ml); * unrelieved toxic reaction caused by any previous anti-cancer treatment higher than ctcae v5.0 grade 1 or above; * routine urine test showed that urinary protein ≥ 2+, and 24-hour urinary protein volume\>1.0g.

Keywords: neoadjuvant peri-operative