Neoadjuvant Treatment of Fruquintinib Combined With Concurrent Chemoradiotherapy for LARC

Rectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05575635
• Other study ID #: HMPL-013-FLAG-C121
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: November 2022
• Est. completion date: November 2025

Study information

• Verified date: October 2022
• Source: Henan Provincial People's Hospital
• Contact: Mingyue Liu, M.D.
• Phone: 18638927799
• Email: liumingyuezz[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: November 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rectal Cancer
• Rectal Neoplasms

Intervention

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)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Henan Provincial People's Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pCR	pathological complete response rate assessed by the investigator	about 2 months
Secondary	MPR	major pathological response rate assessed by the investigator	about 2 months
Secondary	ORR	objective response rate assessed by the investigator	about 2 months
Secondary	R0 resection rate	R0 resection rate	about 2 months
Secondary	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
Secondary	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
Secondary	TRAEs	treatment-related adverse events by CTCAE v5.0	about 6 months