A Study of Nimotuzumab Plus Concurrent Chemoradiotherapy Sequential Maintenance Treatment for Cervical Carcinoma

This is a multicenter, prospective, randomized, double-blind, placebo-controlled clinical study.The trail will enroll 460 subjects (FIGO 2018, stageIB3-IVA)who meet enrollment criteria but do not meet exclusion criteria. According to clinical stage (FIGO 2018 stage, stage IB3-IIB or III-IVA) 、tumor diameter (>4cm or ≤4cm)、 age (≥18 years and < 65 years old or ≥65 years old and ≤80 years old) for stratified randomization. They are divided into experimental group and control group according to 1:1. Patients in the experimental group will receive nimotuzumab 400mg on the basis of concurrent chemoradiotherapy, once a week for 7-8 weeks, and then maintenance treatment once every 2 weeks for 24 weeks. Using placebo(Nimotuzumab injection mimics) in the control group 80 ml on the basis of concurrent chemoradiotherapy, once a week for 7 to 8 weeks, after the maintenance treatment, once every 2 weeks for 24 weeks. Patients with incomplete tumor response assessed by imaging and pathological examination 3 months after radiotherapy can be given 2-4 cycles of adjuvant chemotherapy with cisplatin/carboplatin combined with paclitaxel regimen. Regular imaging examination and survival follow-up were performed after treatment. The primary efficacy end point was progression-free survival.

Inclusion criteria

• 1.Aged 18-80 years old;
• 2.Histologically diagnosed primary cervical squamous cell carcinoma, with clinical stage IB3-IVA (FIGO 2018);
• 3.At least one measurable lesion according to RECIST 1.1;
• 4.Absence of severe hematopoietic dysfunction and heart, lung, liver, kidney dysfunction and immunodeficiency, laboratory test results meet the following criteria: Hemoglobin ≥ 90 g/L; Absolute neutrophil count ≥ 1.5 × 10^9/L and white blood cell count ≥ 3.0 × 10^9/L; Platelet count ≥ 100 × 10^9/L; Aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alanine aminotransferase (ALT) ≤ 2.5 × ULN ; Total bilirubin ≤ 1.5 × ULN; Serum creatinine ≤ 1.0 × ULN;
• 5.ECOG score 0-1 points;
• 6.Women of childbearing potential must have a negative serum or urine HCG within 72 hours prior to enrollment (postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. A pregnancy test is not required for women who have demonstrated tubal ligation); Women of childbearing potential who are willing to take medically recognized contraceptive measures during the trial;
• 7.Compliance is good and informed consent is voluntarily signed.

Exclusion criteria

• 1.Cervical adenocarcinoma and rare pathological types of malignant tumors;
• 2.Previous surgery for cervical cancer, pelvic radiation therapy, systemic chemotherapy, tumor targeted therapy, immunotherapy;
• 3.Ureteral obstruction, inability to place ureteral stent or pyelostomy;
• 4.Pregnant or lactating women;
• 5.Patients with rectovaginal fistula/vaginovesical fistula/uncontrolled vaginal bleeding or at risk of fistula;
• 6.Had undergone major surgery (except biopsy) within 4 weeks prior to randomization;
• 7.Had received a live vaccine within 4 weeks prior to the initial study drug treatment or planned to vaccinate during the study;
• 8.Human immunodeficiency virus (HIV) infection;Active hepatitis B (the quantitative detection result of HBV DNA exceeds the lower limit of detection), or HCV infection (the quantitative detection result of HCV RNA exceeds the lower limit of detection);
• 9.Had the following serious medical conditions: a) Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg), or had experienced a hypertensive crisis; b) Myocardial infarction and unstable angina occurred within 6 months before randomization; c) Decompensated heart failure within three months before enrollment (NYHA class III and IV); d) The presence of severe arrhythmias requiring long-term medical intervention, except in patients with asymptomatic atrial fibrillation with stable ventricular rate; e) Left ventricular ejection fraction (LVEF)<50%; f) The presence of uncontrolled hyperglycemia; g) The presence of uncontrollable infections；
• 10.The presence of active or suspected autoimmune diseases, except for type 1 diabetes、hypothyroidism or skin conditions that do not require systemic treatment (vitiligo、psoriasis or alopecia)；
• 11.Conditions requiring systemic treatment with corticosteroids or other immunosuppressive agents within 14 days before randomization；
• 12.Patients with a history of other malignant tumors (except cured cutaneous basal cell carcinoma);
• 13.Patients with Crohn's disease and ulcerative colitis;
• 14.Patients who are participating in other clinical trials or have stopped clinical trials for less than 4 weeks;
• 15.Patients with known hypersensitivity to Nimotuzumab or its components;
• 16.Patients with contraindications to cisplatin、carboplatin and paclitaxel;
• 17.Patients with neurological or psychiatric disorders affecting cognitive ability;
• 18.Patients whose lesions cannot be treated with intracavitary radiotherapy as assessed by the investigator;
• 19.Any condition that, in the opinion of the Investigator, may be inappropriate for patients in the study.