Rectal Cancer
Conditions
Keywords
neoadjuvant, peri-operative
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.
Interventions
DRUGfruquintinib + 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)
Sponsors
Henan Provincial People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | about 2 months | pathological complete response rate assessed by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | about 2 months | objective response rate assessed by the investigator |
| R0 resection rate | about 2 months | R0 resection rate |
| MPR | about 2 months | major pathological response rate assessed by the investigator |
| OS | about 5 years | OS will be calculated from the date of first administration of study drug to the date of death by any reason. |
| TRAEs | about 6 months | treatment-related adverse events by CTCAE v5.0 |
| DFS | about 3 years | 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. |
Contacts
Primary ContactMingyue Liu, M.D.
Outcome results
None listed