Clinical trial NCT05575635: Neoadjuvant Treatment of Fruquintinib Combined With Concurrent Chemoradiotherapy for LARC
Official title: A Single Arm, Single Center Clinical Study of Fruquintinib Combined With Concurrent Chemoradiotherapy for Neoadjuvant Treatment of Locally Advanced Rectal Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Rectal Cancer
Keywords: neoadjuvant
peri-operative
Lead sponsor: Henan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2022-10-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: pCR
timeFrame: about 2 months
Secondary outcomes:
measure: MPR
timeFrame: about 2 months
measure: ORR
timeFrame: about 2 months
measure: R0 resection rate
timeFrame: about 2 months
measure: DFS
timeFrame: about 3 years
measure: OS
timeFrame: about 5 years
measure: TRAEs
timeFrame: about 6 months
Other outcomes:
Locations:
Study officials:
References: