Nimotuzumab Combined With Chemoradiotherapy Versus Chemoradiotherapy for Local Advanced Cervical Squamous Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
To investigate the efficacy and safety of nimotuzumab combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy in the treatment of local advanced cervical squamous cell carcinoma.

Detailed Description
-----------------
This study adopts a multi-center, randomized controlled, open-label clinical trial design.

Official Title
-----------------
To Investigate the Efficacy and Safety of Nimotuzumab Combined With Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy in the Treatment of Local Advanced Cervical Squamous Cell Carcinoma

Conditions
-----------------
Cervical Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Nimotuzumab
* Drug: Cisplatin
* Radiation: External-beam radiation
* Radiation: Brachytherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18-75 years old; Histologically diagnosed primary cervical squamous cell carcinoma, with clinical stage IB3-IVA (FIGO 2018); At least one measurable lesion according to RECIST 1.1; 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 ≥ 2 × 109/L or white blood cell count ≥ 4.0 × 109/L; Platelet count ≥ 100 × 109/L; Aspartate aminotransferase (AST) ≤ 2.5 × ULN Alanine aminotransferase (ALT) ≤ 2.5 × ULN Total bilirubin ≤ 1.5 × ULN; Serum creatinine ≤ 1.0 × ULN; ECOG score 0-2 points; Expected survival ≥ 3 months; 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); No intrauterine device; Women of childbearing potential who are willing to take medically recognized contraceptive measures during the trial; Compliance is good and informed consent is voluntarily signed. Exclusion Criteria: Cervical adenocarcinoma and rare pathological types of malignant tumors; Previous surgery for cervical cancer, pelvic radiation therapy, systemic chemotherapy, tumor targeted therapy, immunotherapy; Ureteral obstruction, inability to place ureteral stent or pyelostomy; Pregnant or lactating women; Patients with rectovaginal fistula/vaginovesical fistula/uncontrolled vaginal bleeding or at risk of fistula; 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); Patients have a serious underlying condition that precludes safe administration of trial treatment. Including but not limited to active infection requiring systemic drug therapy: decompensated heart failure (NYHA Class III and IV), unstable angina pectoris, acute myocardial infarction within 3 months prior to enrollment; Patients with a history of other malignant tumors (except cured cutaneous basal cell carcinoma); Patients with Crohn's disease and ulcerative colitis; Patients who are participating in other clinical trials or have stopped clinical trials for less than 4 weeks; Patients with known hypersensitivity to Nimotuzumab or its components; Patients with contraindications to cisplatin; Patients with neurological or psychiatric disorders affecting cognitive ability; Patients whose lesions cannot be treated with intracavitary radiotherapy as assessed by the investigator; Other reasons that, in the judgment of the investigator, would make the patient inappropriate for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nimotuzumab+ chemoradiotherapy<br>Patients receive nimotuzumab combined with cisplatin and undergo external-beam radiation and brachytherapy. | Drug: Nimotuzumab<br>* Patients receive Nimotuzumab 400 mg each time, once a week, slow intravenous drip, for a total of 6 weeks.<br>* Other names: EGFR monoclonal antibody;Drug: Cisplatin<br>* Patients receive 40 mg/m2, d1, 7 days as 1 treatment cycle, 6 treatment cycles in total<br>* Other names: Cisplatin injection;Radiation: External-beam radiation<br>* Patients undergo IMRT/VMAT radiotherapy with pelvic and/or extended field irradiation at a total dose of 45 - 50.4 Gy; 1.8 - 2.0 Gy/f, 25 - 28 f.<br>Radiation: Brachytherapy<br>* Patient undergo Brachytherapy with high dose rate, with a total dose of 30-40 Gy and a cumulative dose of 80   85 Gy at point A/HRCTV D90; if the tumor diameter is ≥ 4 cm, the cumulative dose of ≥ 87 Gy at point A/HRCTV D90.<br>|
| Active Comparator: Chemoradiotherapy<br>Patients receive cisplatin and undergo external-beam radiation and brachytherapy | Drug: Cisplatin<br>* Patients receive 40 mg/m2, d1, 7 days as 1 treatment cycle, 6 treatment cycles in total<br>* Other names: Cisplatin injection;Radiation: External-beam radiation<br>* Patients undergo IMRT/VMAT radiotherapy with pelvic and/or extended field irradiation at a total dose of 45 - 50.4 Gy; 1.8 - 2.0 Gy/f, 25 - 28 f.<br>Radiation: Brachytherapy<br>* Patient undergo Brachytherapy with high dose rate, with a total dose of 30-40 Gy and a cumulative dose of 80   85 Gy at point A/HRCTV D90; if the tumor diameter is ≥ 4 cm, the cumulative dose of ≥ 87 Gy at point A/HRCTV D90.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year progression-free survival (PFS) | The rate of patient without progress disease in 3 years after treatment | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year overall survival (OS) | The rate of patient alive in 3 years after treatment | up to 3 years | 
| Complete response rate (CRR) | Percentage of subjects in this group who achieve complete response by imaging assessment from the end of treatment to disease progression. | 3 months later after treatment | 
| Objective response rate (ORR) | The percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment. | 3 months later after treatment | 
| Incidence and severity of acute adverse events | Number and grade of participants with adverse events | up to 3 months complete treatment |