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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rectal Cancer
• Intervention / Treatment: Drug: fruquintinib + concurrent radiotherapy + chemotherapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingyue Liu, M.D.; Phone Number: 18638927799; Email: liumingyuezz@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: fruquintinib + mFOLFOX6 + radiotherapy

Drug: 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Henan Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2022
• Primary Completion (ANTICIPATED): May 1, 2024
• Study Completion (ANTICIPATED): November 1, 2025

Study Registration Dates

• First Submitted: October 8, 2022
• First Submitted That Met QC Criteria: October 8, 2022
• First Posted (ACTUAL): October 12, 2022

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 8, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: neoadjuvant; peri-operative
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms
• Other Study ID Numbers: HMPL-013-FLAG-C121

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No