Study of Nimotuzumab Combined With Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

Study Overview
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Brief Summary
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The purpose of this phase II trial is to determine the feasibility and efficacy of nimotuzumab combined with concurrent chemoradiotherapy for initially inoperable locally advanced cervical squamous cell carcinoma.

Detailed Description
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This phase II trial is studying how well giving nimotuzumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as nimotuzumab, a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody that is approved in many countries for the treatment of EGFR-positive cancers. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Nimotuzumab also stop the growth of cervical cancer by increasing the effect of chemotherapy. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nimotuzumab together with radiation therapy and cisplatin may kill more tumor cells.

Official Title
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Efficacy and Safety of Nimotuzumab Combined With Radiotherapy and Concurrently Cisplatin in Patients With Stage IIB-IVA Cervical Squamous Cell Carcinoma

Conditions
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Neoplasms, Cervical Adenosquamous Cell Carcinoma, Cervical Squamous Cell Carcinoma in Situ, Stage IB Cervical Cancer, Stage IIA Cervical Cancer, Stage IIB Cervical Cancer, Stage III Cervical Cancer, Stage IVA Cervical Cancer

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: Cisplatin
* Radiation: external-beam radiation
* Radiation: brachytherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All volunteers will sign the informed consent. Histologically confirmed squamous cell of the uterine cervix, EGFR(+). The FIGO stage (IIB-IVA) and was not available for surgical treatment. There is at least one tumor lesion that is measurable by RECIST. During the study, contraception should be ensured. Karnofsky performance status >60. WBC >= 3,000/mm^3 Absolute granulocyte count >= 1,500/mm^3 Platelet count >= 100,000/mm^3 INR < 1.5 Total bilirubin =< 1.5 mg/dL Serum creatinine =< 1.5 mg/dL AST and ALT =< 2.5 times upper limit of normal (ULN) Serum calcium =< 1.3 times ULN Hemoglobin >= 9g/dL (transfusion allowed) Exclusion Criteria: Positive para-aortic lymph nodes or positive lymph nodes beyond pelvic Prior invasive malignancy (except nonmelanomatous skin cancer) Contraindication of chemotherapy; Rare pathological subtype; Cervical cancer patients underwent hysterectomy, laparoscopic surgery or systemic chemotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>Patients receive nimotuzumab combined with cisplatin and undergo external-beam radiation and brachytherapy as the patients in experimental group. | Drug: Nimotuzumab<br>* Patients receive nimotuzumab IV over 90 minutes on days 1, 8, 15, 22, 29, 36,43.<br>* Other names: EGFR monoclonal antibody;Drug: Cisplatin<br>* Patients undergo cisplatin, 25-40 mg/m2 a week for 4 or 5weeks<br>* Other names: Cisplatin injection;Radiation: external-beam radiation<br>* Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45-50.4Gy<br>* Other names: pelvic EBRT;Radiation: brachytherapy<br>* high-dose rate brachytherapy,6Gy once weekly,for a total of 24-30Gy<br>* Other names: high-dose rate brachytherapy;|
| Active Comparator: control group<br>Patients receive cisplatin and undergo external-beam radiation and brachytherapy as the patients in control group. | Drug: Cisplatin<br>* Patients undergo cisplatin, 25-40 mg/m2 a week for 4 or 5weeks<br>* Other names: Cisplatin injection;Radiation: external-beam radiation<br>* Patients undergo pelvic EBRT once daily, 5 days a week, for 5 weeks for a total of 45-50.4Gy<br>* Other names: pelvic EBRT;Radiation: brachytherapy<br>* high-dose rate brachytherapy,6Gy once weekly,for a total of 24-30Gy<br>* Other names: high-dose rate brachytherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progress free survival rate | The rate of patient without progress disease in 3 years after treatment | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival rate | The rate of patient alive in 3 years after treatment | 3 years | 
| Local area control rate. | The rate of patient without recurrence in 3 years after treatment | 3 years | 
| No distant metastatic survival. | The rate of patient without metastatic disease in 3 years after treatment | 3 years | 
| objective response rate | the percentage of patients who experienced complete or partial cancer shrinkage or disappearance after treatment. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical Cancer, Radiation Therapy, Chemotherapy, Nimotuzumab, Cisplatin