Neoadjuvant Treatment of Fruquintinib Combined With Concurrent Chemoradiotherapy for LARC

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Rectal Cancer

Intervention / Treatment
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* Drug: fruquintinib + concurrent radiotherapy + chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fruquintinib + mFOLFOX6 + radiotherapy<br>fruquintinib + mFOLFOX6 + radiotherapy | Drug: fruquintinib + concurrent radiotherapy + chemotherapy<br>* mFOLFOX6: The mFOLFOX6 regimen will be administered on Day 1 of each treatment cycle. This regimen consists of oxaliplatin 85 mg/m2 IV given over 2 hours, leucovorin 400 mg/m2 IV given over 2 hours, and fluorouracil 400 mg/m2 IV bolus, followed by fluorouracil 1200 mg/m2 per day for 2 days, continuous infusion. fruquintinib: 3mg/d, qd po, for 7 weeks continuously. Radiation Therapy: radiation 45.0 50.0 Gy (1.8-2.0 Gy/day or 25 fractions weeks 3-7)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR | pathological complete response rate assessed by the investigator | about 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MPR | major pathological response rate assessed by the investigator | about 2 months | 
| ORR | objective response rate assessed by the investigator | about 2 months | 
| R0 resection rate | R0 resection rate | about 2 months | 
| DFS | DFS (Disease-free survival) will be calculated from the date of first administration of study drug to the date of recurrence or death by any reason. | about 3 years | 
| OS | OS will be calculated from the date of first administration of study drug to the date of death by any reason. | about 5 years | 
| TRAEs | treatment-related adverse events by CTCAE v5.0 | about 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoadjuvant, peri-operative