Study of Nimotuzumab Combined With IMRT in Elder Patients With Cervical Squamous Cell Carcinoma

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of Nimotuzumab combined with IMRT in elder patients with locally advanced cervical squamous cell carcinoma

Detailed Description
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This is a perspective, multi-center, open-label and single arm study.

Official Title
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A Perspective, Multi-center, Single Arm Study of Nimotuzumab Combined With IMRT in Elder Patients With Cervical Squamous Cell Carcinoma

Conditions
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Cervical Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Nimotuzumab
* Radiation: EBRT combined with brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age≥65 years old Histologically confirmed primary cervical squamous cell carcinoma in stage IB3-IVA (FIGO 2018) At least one measurable lesion according to RECIST 1.1 guideline Patients are intolerant to or refuse chemotherapy. No serious hematopoietic dysfunction, nor abnormal heart, lung, liver and kidney function, nor immunity deficiency. And the results of lab test meet the following criteria: Hemoglobin ≥90g/L Absolute count of neutrophils≥2×109/L orwhite blood cell count≥4.0×109/L； Platelet count≥100×109/L； AST≤2.5×ULN ALT≤2.5×ULN TBIL≤1.5×ULN； Serum creatinine≤1.5×ULN or CrCl> 60 mL/min(according toCockcroft-Gault): Serum creatinine≤1.5×ULN Female CrCl=(140-Age)×Weight（kg）×0.85 / (72×Scr mg/dl) ECOG score 0-2 Expectancy of life is at least 3 months. Eligible for pelvic MRI examination. The patients voluntarily received nimotuzumab combined with radiotherapy. Patients can comply with the protocol and are willing to sign informed consent. Exclusion Criteria: Patients who have received treatment for cervical cancer, including surgery, radiotherapy, chemotherapy, targeted therapy and immunotherapy Patients who have bilateral ureteral obstruction, who cannot be placed ureteral stents or perform pyelostomy. Patients with rectovaginal fistula/vaginovesical fistula/uncontrolled vaginal bleeding or with fistula risk. .4)Patients infected with HIV. 5)Active hepatitis B (HBV DNA quantitative test results exceed the detection threshold), or HCV infection (HCV RNA quantitative test results exceed the detection threshold) 6)Patients with severe underlying disease that makes it possible to safely receive the treatment. And the severe underlying disease include but not limited to active infections requiring systemic medication, decompensated heart failure (NYHA grade III and IV), unstable angina pectoris, and acute myocardial infarction occurred within the first 3 months of enrollment. 7)Patients with a history of prior malignancy other than cured basal cell carcinoma of the skin. 8)Patients with Crohn's disease and ulcerative colitis. 9)Patients are allergic to Nimotuzumab or its compounds. 10)Patients with neurological or psychiatric abnormalities that affect cognitive ability. 11)Intracavitary brachytherapy cannot be performed that was assessed by the investigator. 12)Other factors were assessed by investigators to be unsuitable to this study.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| observation group<br>All patients will be treated with Nimotuzumab combined with radiotherapy. | Drug: Nimotuzumab<br>* Patients receive Nimotuzumab: 200mg, intravenous infusion, weekly for 6 weeks.<br>Radiation: EBRT combined with brachytherapy<br>* IMRT/VMAT are adopted. A total dose of 45-50.4 Gy, 1.8 2.0Gy/f, 25  28F in pelvic and/or extension filed. For patients with metastasis in pelvic lymph node and abdominal para-aortic lymph node, the dose of radiation in local lesion will be increased to 60 66Gy. For patients at stage IIIB, concurrent radiation will be given in parametrial extension or in the late course the dose will be increased to 60Gy. Brachytherapy: Three dimensional high dose rate brachytherapy is used with HR-CTV D90 cumulative dose of 80 85Gy (EQD2); If the tumor diameter is ≥4cm, HR-CTV D90 cumulative dose is ≥87Gy (EQD2). Brachytherapy combined with external beam radiotherapy will be completed within 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate(CRR) | The percentage of subjects who achieve complete response by imaging assessment from the end of the 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 treatment | 
| 3-year overall survival(OS) | The rate of patient alive in 3 years after treatment | up to 3 years | 
| The change of tumor related markers | the correlation of the value of SCC，Cyfra 21-1 and therapeutic effect [The changes of serum tumor markers (such as SCC-Ag and CYFRA21-1) were observed before and after treatment] | up to 3 years | 
| The change of cervical tumor | the change of the volume of the cervical tumor at diagnosis and before brachytherapy | At diagnosis and before brachytherapy | 
| QUALITY OF LIFE(QoL) | Quality of life assessed by EORTC QLQ-CX 24 [EORTC QLQ-CX 24 is a specific quality of life assessment scale based on EORTC QLQ-C 30, with 24 items] | up to 3 years | 
| SAFETY | Including severity of adverse events, the incidence of adverse events and serious adverse events. Adverse events should be reported and graded according to CTCAE version 5.0 | up to 3 years |