Concurrent and Adjuvant Nimotuzumab Combined With Induction Chemotherapy Plus Chemoradiation in Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Nimotuzumab is an IgG1 humanized monoclonal antibody that recognized an epitope located in the extra cellular domain of the human epidermal growth factor receptor (EGFR). Nimotuzumab has been granted approval for use in squamous cell carcinoma of head and neck (SCCHN), glioma and nasopharyngeal cancer in different countries. This is a multi-center, randomized controlled trial, with the purpose to evaluate the therapeutic efficacy and safety of nimotuzumab combined with induction chemotherapy plus chemoradiation and adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma.

Official Title
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Nimotuzumab Combined With Induction Chemotherapy Plus Chemoradiation and Adjuvant Therapy in Locoregionally Advanced Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma by AJCC V8 Stage

Intervention / Treatment
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* Drug: Nimotuzumab
* Drug: Gemcitabine
* Drug: Cisplatin
* Radiation: Intensity-modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18 to 70. Pathological type: non-keratinizing carcinoma (World Health Organization criteria). Diagnosed with LANPC (stage III-IV, except for patients with T3N0)) according to the 8th edition clinical staging system of the American Joint Committee on Cancer [AJCC]/Union for International Cancer Control [UICC]. ECOG performance score: 0 to 1. Primary lesions can measurable. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and creatinine clearance rate ≥ 50 ml/min (Cockcroft-Gault formula). Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule. Exclusion Criteria: Primary lesions or lymph node have been operated (except of operation for biopsy). Previous Received other anti EGFR monoclonal antibody treatment;Previous chemotherapy or immunization therapy. Other malignant tumor. Participation in other interventional clinical trials within 1 month. History of Serious lung or heart disease. Pregnant or breast-feeding women and women who refused to take contraceptive method. Drug abuse or alcohol addiction. History of serious allergic or allergy. Refused or can't signed informed consent form. Other patients who are considered ineligible for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Nimotuzumab arm<br>Patients will receive induction chemotherapy with nimotuzumab (200mg/w,weekly plus gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 2 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) will be given. Concurrent nimotuzumab (200mg/w,weekly, 6-7 weeks) and cisplatin (100mg/m2,every 3 weeks for 3cycles )will be administered during IMRT. After 4-6 weeks of the completion of IMRT, adjuvant nimotuzumab (200mg ) will be given every 3 weeks for 8 cycles. | Drug: Nimotuzumab<br>* Drug: Nimotuzumab Experimental: Nimotuzumab arm Induction chemotherapy:Nimotuzumab 200mg will be given weekly for 6 cycles, started on day 1 of induction chemotherapy. Concurrent chemotherapy: Nimotuzumab 200mg/week in concurrent with IMRT. Adjuvant therapy: Nimotuzumab (200mg ) will be given every 3 weeks for 8 cycles. Active Comparator: Control Nimotuzumab 200mg/week in concurrent with IMRT .<br>* Other names: BIOMAb EGFR;Drug: Gemcitabine<br>* Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 2 cycles<br>* Other names: GEM;Drug: Cisplatin<br>* Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles. Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles.<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* Definitive IMRT of 68-78 Gy, 30-33 fractions, 5 fractions/week, 1 fraction/day<br>* Other names: IMRT;|
| Active Comparator: Control<br>Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 2 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) will be given. Concurrent nimotuzumab (200mg/w,weekly, 6-7 weeks) and cisplatin (100mg/m2,every 3 weeks for 3cycles )will be administered during IMRT. | Drug: Nimotuzumab<br>* Drug: Nimotuzumab Experimental: Nimotuzumab arm Induction chemotherapy:Nimotuzumab 200mg will be given weekly for 6 cycles, started on day 1 of induction chemotherapy. Concurrent chemotherapy: Nimotuzumab 200mg/week in concurrent with IMRT. Adjuvant therapy: Nimotuzumab (200mg ) will be given every 3 weeks for 8 cycles. Active Comparator: Control Nimotuzumab 200mg/week in concurrent with IMRT .<br>* Other names: BIOMAb EGFR;Drug: Gemcitabine<br>* Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 2 cycles<br>* Other names: GEM;Drug: Cisplatin<br>* Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles. Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles.<br>* Other names: DDP;Radiation: Intensity-modulated radiotherapy<br>* Definitive IMRT of 68-78 Gy, 30-33 fractions, 5 fractions/week, 1 fraction/day<br>* Other names: IMRT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival(OS) | Overall survival is measured from day of diagnosis until death due to any cause or the latest known date alive.OS will be measured by the Method of Kaplan and Meier. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor control probability (TCP) | Tumor control probability is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: at least 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. | 5 years | 
| Disease-free survival(DFS) | DFS is defined as the time from randomization to the first documented disease progression or death due to disease progression per RECIST 1.1. DFS will be measured by the Method of Kaplan and Meier. | 5 years | 
| Locoregional failure-free survival(LRRFS) | LRRFS is defined as the time from randomization to the date of locoregional relapse per RECIST 1.1. LRRFS will be measured by the Method of Kaplan and Meier. | 5 years | 
| Distant Metastasis-free survival(DMFS) | DMFS is defined as the time from randomization to the date of first distant metastasis. DMFS will be measured by the Method of Kaplan and Meier. | 5 years | 
| Incidence rate of investigator-reported adverse events (AEs) | Analysis of investigator-reported adverse events (AEs) are based on treatment-related AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. AEs are evaluated by investigators according to the Common Terminology Criteria for Adverse Events, version 5.0 and radiation therapy oncology group (RTOG) toxicity criteria. | 5 years | 
| Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) | Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0) before treatment, during treatment, after treatment. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nimotuzumab, Nasopharyngeal Carcinoma, Induction Chemotherapy, Chemoradiation, Adjuvant Therapy