Locally Advanced Colorectal Cancer
Conditions
Keywords
Serplulimab, CAPOX, Bevacizumab
Brief summary
This is an exploratory study to evaluate the efficacy and safety of neoadjuvant therapy with serplulimab combined with CAPOX and bevacizumab for patients with locally advanced colorectal cancer. The primary endpoint is pathological complete response (pCR). Secondary efficacy endpoints include major pathological response (MPR), R0 resection rate, tumor down-staging, objective response rate (ORR), disease-free survival (DFS), and quality of life, to demonstrate clinical benefit of this combination regimen in the target patient population.
Interventions
DRUGSerplulimab
Anti-PD-1 monoclonal antibody, administered intravenously as neoadjuvant therapy.
DRUGCAPOX
Combination chemotherapy regimen consisting of capecitabine plus oxaliplatin, administered intravenously as neoadjuvant therapy.
DRUGBevacizumab
Anti-VEGF monoclonal antibody, administered intravenously as neoadjuvant therapy.
Sponsors
Xijing Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Voluntarily provide written informed consent prior to screening. * Male or female subjects aged ≥18 years. * At least one measurable lesion per RECIST 1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. * Histologically or pathologically confirmed locally advanced rectal adenocarcinoma, cT3/cT4N+M0 stage per AJCC/UICC 8th edition, with distance from anal verge ≤10 cm. Diagnosis is confirmed by contrast-enhanced CT/MRI, supplemented by colonoscopy and diagnostic laparoscopy if necessary; no prior anti-tumor treatment. * Scheduled for surgical resection following neoadjuvant therapy based on clinical staging. * Expected survival of more than 3 months. * No emergency indications such as bowel obstruction, bleeding or perforation. * Adequate major organ function as follows (no blood transfusion, granulocyte-colony stimulating factor (G-CSF) or other hematopoietic growth factor support within 14 days prior to screening): 1. Hematology: Absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin ≥90 g/L, white blood cell count ≥3.5×10⁹/L. 2. Liver function: ALT and AST ≤2.5×ULN; total bilirubin ≤1.5×ULN (≤3×ULN for patients with Gilbert syndrome). 3. Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min. 4. Coagulation function: APTT, INR, PT ≤1.5×ULN.
Exclusion criteria
* Prior anti-tumor therapy including chemotherapy, radiotherapy, hormonal therapy or molecular-targeted therapy. * Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibodies, or other agents targeting T-cell co-stimulatory or immune-checkpoint pathways. * History of other malignant tumors within 5 years or concurrent other malignancies, except for cured carcinoma in situ of cervix, non-melanoma skin cancer, or other malignancies with ≥5 years disease-free survival after curative treatment. * Peripheral neuropathy ≥Grade 2 per NCI-CTCAE v5.0. * Known active central nervous system metastases and/or carcinomatous meningitis. * History of severe hypersensitivity reaction (NCI-CTCAE v5.0 ≥Grade 3) to anti-PD-1 monoclonal antibodies, other monoclonal antibodies, oxaliplatin, S-1 or related compounds. * History of hereditary bleeding disorders or coagulopathy with high bleeding risk. * Major surgical procedure within 4 weeks prior to screening. * Not recovered from prior surgical complications with residual toxicity \>Grade 1 (NCI-CTCAE v5.0), excluding alopecia and fatigue. * Requirement for immunosuppressive medication within 2 weeks before screening or during study treatment, except for: 1. Intranasal, inhaled, topical or intra-articular corticosteroids. 2. Physiological-dose systemic corticosteroids (≤10 mg/day prednisone or equivalent). 3. Short-term (≤7 days) corticosteroids for prophylaxis or treatment of non-autoimmune allergic conditions. * Active or history of recurrent autoimmune disease. * History of interstitial lung disease or non-infectious pneumonitis. * Known active tuberculosis (Mycobacterium tuberculosis) infection. * Human immunodeficiency virus (HIV) positive, other acquired or congenital immunodeficiency, history of organ transplantation or stem-cell transplantation. * Hepatitis B or C virology findings at screening meeting any of the following: 1. HBsAg-positive with HBV-DNA ≥10⁴ copies/mL or ≥2000 IU/mL (antiviral therapy may be administered for HBV carriers at investigator's discretion). 2. Active hepatitis C: HCV-antibody-positive with detectable HCV-RNA above assay lower limit. * Active or uncontrolled infection requiring systemic therapy within 2 weeks prior to screening. * Receipt of live-virus vaccine within 4 weeks prior to screening. * Bowel obstruction, or history of inflammatory bowel disease, extensive bowel resection with chronic diarrhea, Crohn's disease, ulcerative colitis or chronic diarrhea. * Lactating females, or females planning pregnancy during study treatment or within 6 months after treatment completion. * Subjects (fertile males, females and their male partners) unwilling to use effective contraception during study treatment and for 6 months after treatment completion. * Any other condition that, in the investigator's opinion, would compromise study compliance or outcome assessment, making the subject unsuitable for study participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection) | Percentage of patients who achieve pathological complete response, defined as no residual viable tumor cells in the resected surgical specimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathological Response (MPR) Rate | Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection) | Percentage of patients with ≤10% residual viable tumor cells in the resected surgical specimen. |
| R0 Resection Rate | Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection) | Proportion of patients who undergo complete R0 surgical resection. |
| Tumor Down-staging Rate | Up to 6 weeks after completion of neoadjuvant therapy (at surgical resection) | Proportion of patients with pathological tumor down-staging compared with baseline clinical staging. |
| Objective Response Rate (ORR) | Up to 6 weeks after completion of neoadjuvant therapy (prior to surgical resection) | Proportion of patients with complete or partial response assessed by imaging according to RECIST criteria. |
| Disease-Free Survival (DFS) | Up to 36 months after surgical resection | Time from randomization/surgery to disease recurrence or death from any cause. |
Contacts
CONTACTJinqiang Liu
PRINCIPAL_INVESTIGATORLiu Hong
Xijing Hospital of Digestive Diseases, Xijing Hospital, Air force Medical University, Changlexi ST 15, Shaanxi Province, 710032, China
Outcome results
None listed