Neoadjuvant Treatment of Fruquintinib Combined With Concurrent Chemoradiotherapy for LARC

NCT ID: NCT05575635

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-30
• Study Completion Date: 2025-11-30

Brief 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.

Detailed Description

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.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

fruquintinib + mFOLFOX6 + radiotherapy

fruquintinib + mFOLFOX6 + radiotherapy

Group Type: EXPERIMENTAL

fruquintinib + concurrent radiotherapy + chemotherapy

Intervention Type: DRUG

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)

Interventions

fruquintinib + concurrent radiotherapy + chemotherapy

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)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Henan Provincial People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Liu Ming Yue

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Mingyue Liu, M.D.

Role: CONTACT

liumingyuezz@163.com

18638927799

Other Identifiers

HMPL-013-FLAG-C121

Identifier Type: -

Identifier Source: org_study_id