A Clinical Study Comparing Chemotherapy Combined With PD-1 Inhibitor Versus Concurrent Chemoradiotherapy in Cervical Cancer Patients With Positive Lymph Nodes After Surgery: A Multicenter Randomized Controlled Clinical Trial

CIT Trial for Cervical Cancer Patients

This study aims to conduct a prospective, multicenter, randomized controlled trial targeting patients with cervical cancer who have been pathologically confirmed to have lymph node metastasis after surgery. The study will proceed as follows:

Patients who have undergone cervical cancer surgery and have been pathologically confirmed to have positive retroperitoneal lymph nodes will be selected according to the inclusion and exclusion criteria. Their clinical and pathological data will be collected. These patients will be randomly assigned in a 1:1 ratio to two groups: the chemotherapy-immunotherapy (chemo-immunotherapy) group and the concurrent chemoradiotherapy group.

The study will compare the two treatment strategies by evaluating tumors' 3-year recurrence rate, distant metastasis rate, and overall survival prognosis in patients. The primary endpoints are the 3-year recurrence rate and distant metastasis rate. Secondary endpoints include the 3-year local recurrence rate, progression-free survival (PFS), and overall survival (OS). Additionally, the study will assess differences in complications, toxic side effects of chemotherapy and radiotherapy, and quality of life between the two groups to determine the value of chemo-immunotherapy in treating this patient population.

In addition, biological tissue samples from 50 patients in the chemo-immunotherapy cohort will be collected for multi-omics analysis and detection of immune-related biomarkers. Using bioinformatics methods, the study will analyze the differences in cellular immune subtypes and immune-related biomarkers between patients who benefit from the treatment and those who do not. This analysis aims to clarify the therapeutic efficacy of chemo-immunotherapy in patients with postoperative lymph node metastasis after cervical cancer surgery and to identify biomarkers and immune markers associated with treatment benefits.

Inclusion Criteria:

1. Patients with cervical squamous cell carcinoma, adenocarcinoma (usual type), or adenosquamous carcinoma who have been pathologically confirmed to have positive retroperitoneal lymph nodes after radical surgery for cervical cancer, i.e., patients with stage IIIC1p and IIIC2p cervical cancer (FIGO 2018);
2. Positive expression of PD-L1 in pathological examination, i.e., Combined Positive Score (CPS) ≥1;
3. Patients aged ≥18 years and ≤70 years;
4. ECOG performance status score ≤1;
5. Laboratory tests: White blood cell count (WBC) ≥3.5×10^9/L, neutrophil count (NEU) ≥1.5×10^9/L, platelet count (PLT) ≥100×10^9/L, serum total bilirubin ≤1.5 times the upper limit of normal, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤1.5 times the upper limit of normal, serum blood urea nitrogen (BUN) ≤1.5 times the upper limit of regular or creatinine clearance rate ≥50 mL/min (creatinine clearance rate can be calculated using the Cockcroft-Gault formula, the Chronic Kidney Disease Epidemiology Collaboration formula, or the Modification of Diet in Renal Disease formula);
6. Good compliance of the subjects, who can follow the protocol for efficacy follow-up and adverse events/reactions;
7. Subjects voluntarily sign the informed consent form, including adherence to the requirements and restrictions listed in the informed consent form and this protocol.

Exclusion Criteria:

1. Postoperative pathology indicates positive parametrial involvement or positive surgical margins;

2. Incomplete radical surgery;

3. Postoperative imaging confirms the presence of residual target lesions;

4. Any active autoimmune disease or a history of autoimmune disease requiring systemic treatment, including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, thyroid dysfunction, and asthma requiring intervention with bronchodilators;

5. Previous treatment with immune checkpoint inhibitors, including but not limited to other anti-PD-1 and anti-PD-L1 antibodies; known allergy to any component of the study medication or other monoclonal antibodies;

6. History of human immunodeficiency virus (HIV) infection, active hepatitis B (HBV-DNA ≥ 2000 IU/mL or 10⁴ copies/mL), or hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay method);

7. Receipt of immunosuppressive drugs or systemic corticosteroid therapy for immunosuppressive purposes within 2 weeks before the study drug administration (dose >10 mg/day of prednisone or equivalent);

8. Diagnosis of another primary malignancy within 5 years before the first use of the investigational drug.

9. Use any other investigational drug/treatment from another clinical trial within 4 weeks before randomization or concurrent participation in another interventional clinical trial. Participation in observational, non-interventional clinical trials is permitted;

10. Pregnant or breastfeeding female patients;

11. Uncontrolled concomitant diseases, including but not limited to:

    • Cardiovascular diseases: New York Heart Association (NYHA) functional class II or higher, severe/unstable angina, myocardial infarction within ≤6 months before study drug administration, or significant arrhythmias requiring medication or intervention;
    • Uncontrolled hypertension;
    • Cerebrovascular events or central nervous system disorders within ≤6 months before study drug administration, or patients with abnormal mental status;
    • Hematologic disorders: Coagulopathy (INR > 2.0, PT > 16 seconds), bleeding tendency, or ongoing thrombolytic or anticoagulant therapy;
    • Hepatic or renal developmental abnormalities or history of surgery;
    • Any active infection requiring systemic antimicrobial therapy within 14 days before the first dose of the study drug;

12. Receipt of any live or attenuated vaccines within 4 weeks before the first dose of the study drug. Administration of seasonal inactivated influenza vaccine is permitted;

13. Patients who have previously undergone allogeneic bone marrow transplant or solid organ transplantation;

14. History of drug and/or alcohol abuse;

15. Patients deemed by the investigator unlikely to comply with study procedures, restrictions, and requirements are not eligible for participation in this study.