Neoadjuvant Treatment of Fruquintinib Combined With Concurrent Chemoradiotherapy for LARC

A Single Arm, Single Center Clinical Study of Fruquintinib Combined With Concurrent Chemoradiotherapy for Neoadjuvant Treatment of Locally Advanced Rectal Cancer

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.

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.