Cisplatin Plus Docetaxel Versus Cetuximab, Cisplatin, and Docetaxel in Metastatic Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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This is a Phase Ⅲ randomized, controlled, multi-center, trial comparing cisplatin plus docetaxel to cetuximab, cisplatin, and docetaxel induction chemotherapy followed by concurrent chemoradiation in previously untreated patients metastatic nasopharyngeal carcinoma (mNPC) to determine whether the addition of cetuximab to induction chemotherapy and chemoradiation could improve therapeutic efficacy in mNPC, and investigate predictive and prognostic factors for mNPC.

Official Title
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Phase Ⅲ Randomized Trial of Cisplatin Plus Docetaxel Versus Cetuximab, Cisplatin, and Docetaxel Induction Chemotherapy Followed by Concurrent Chemoradiation in Previously Untreated Patients Metastatic Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Cisplatin
* Drug: Docetaxel
* Drug: Capecitabine
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed nasopharyngeal carcinoma Untreated metastatic nasopharyngeal carcinoma (stage ⅣC according to the 7th American Joint Committee on Cancer staging system and stage ⅣB according to the Chinese 2008 staging system for nasopharyngeal carcinoma) Patients must have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy of at least 6 months Absolute neutrophil count (ANC) >=1.5×10^9/L Platelets >= 80×10^9/L Hemoglobin >= 90 g/l Bilirubin <= 1.5 × upper limit of normal (ULN) Aminopherases ( alanine transaminase and aspartate aminotransferase) <= 2.5 × ULN (without liver metastasis) or <= 5.0 × ULN (with liver metastasis) Creatinine <=ULN International normalized ratio (INR) of prothrombin time (PT) <= 1.5 × ULN The pregnancy tests of women of childbearing potential should be negative before treatment Women of childbearing potential and sexually active males must adopt efficient contraception methods while on treatment and for six months after the completion of the treatment Patients should understand and are willing to participate in the study. Inform consent form is supposed to obtained before treatment Exclusion Criteria: Prior radiotherapy of target lesions Prior systemic chemotherapy and/or targeted therapy Brain metastasis Concurrent other malignancies Severe or active infectious disease requiring systemic antibiotics or antiviral, antifungal treatment Active tuberculosis Severe cardiovascular disease, including uncontrolled hypertension, unstable angina, myocardial infarction in the past 6 months, congestive heart failure with cardiac function grade Ⅲ to Ⅳ based on New York Heart Association cardiac functional grading, serious arrhythmia, or pericardial effusion Co-existing mental disease that would preclude full compliance with the study Females are pregnant or breast feeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 |
| --- | --- |
| Active Comparator: cisplatin and docetaxel<br>Induction chemotherapy: Patients receive cisplatin and docetaxel intravenously on day 1 repeated every 3 weeks for 6 cycles. Concurrent chemoradiation: Patients who achieve complete response or partial response receive radiotherapy for primary and/or metastatic lesions with concurrent cisplatin 30mg/m^2 intravenously every week. Maintenance treatment: Capecitabine will be given at a dose of 1000mg/m^2 orally twice a day starting on day 1 and continuing for days 1 to 14 of each 21 day cycle for at least 2 years or until progression. | Drug: Cisplatin<br>* 75mg/m^2 intravenously on day 1 of each 21 day cycle for 6 cycles of induction chemotherapy.30 mg/m^2 intravenously every week concurrent with radiotherapy.<br>Drug: Docetaxel<br>* 75mg/m^2 intravenously on day 1 of each 21 day cycle for 6 cycles of induction chemotherapy.<br>* Other names: Taxotere;Drug: Capecitabine<br>* 1000mg/m^2 orally twice a day, days 1 to 14 of each 21 day cycle for at least 2 years or until progression following concurrent chemoradiation.<br>* Other names: Xeloda;Radiation: Radiotherapy<br>* 60-66 Gy if complete response or 66-70 Gy if partial response following induction chemotherapy.<br>|
| Experimental: cetuximab, cisplatin, and docetaxel<br>Induction chemotherapy: Patients receive cetuximab 400mg/m^2 intravenously over at least 120 minutes on day 1 followed by 250 mg/m^2 intravenously over at least 60 minutes every week. Cisplatin and docetaxel will be administered intravenously on day 2 repeated every 3 weeks for 6 cycles. Concurrent chemoradiation: Patients who achieve complete response or partial response receive radiotherapy for primary and/or metastatic lesions with concurrent cetuximab 250mg/m^2 intravenously followed by cisplatin 30mg/m^2 intravenously every week. Maintenance treatment: Capecitabine will be given at a dose of 1000mg/m^2 orally twice a day starting on day 1 and continuing for days 1 to 14 of each 21 day cycle for at least 2 years or until progression. | Drug: Cetuximab<br>* 400 mg/m^2 intravenously on day 1,then 250 mg/m^2 intravenously every week of each 21 day cycle for 6 cycles of induction chemotherapy.250 mg/m^2 intravenously every week concurrent with radiotherapy.<br>* Other names: Erbitux;Drug: Cisplatin<br>* 75mg/m^2 intravenously on day 1 of each 21 day cycle for 6 cycles of induction chemotherapy.30 mg/m^2 intravenously every week concurrent with radiotherapy.<br>Drug: Docetaxel<br>* 75mg/m^2 intravenously on day 1 of each 21 day cycle for 6 cycles of induction chemotherapy.<br>* Other names: Taxotere;Drug: Capecitabine<br>* 1000mg/m^2 orally twice a day, days 1 to 14 of each 21 day cycle for at least 2 years or until progression following concurrent chemoradiation.<br>* Other names: Xeloda;Radiation: Radiotherapy<br>* 60-66 Gy if complete response or 66-70 Gy if partial response following induction chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Progression-free survival was defined as the time from date of randomization until the date of first documented progression, date of death from any cause, or date of last assessment, whichever came first. All eligible and treated patients were included in the analysis. | From date of randomization until the date of first documented progression, date of death from any cause, or date of last assessment, whichever came first, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | Event-free survival was defined as the time from date of randomization until the date of first documented progression, date of death from any cause, date of introduction of a new treatment without evidence of progression or relapse, or date of last assessment, whichever came first. All eligible and treated patients were included in the analysis. | From date of randomization until the date of first documented progression, date of death from any cause, date of introduction of a new treatment, or date of last assessment, whichever came first, assessed up to 5 years. | 
| Disease-free Survival | Disease-free survival was defined as the time from date of attainment a complete response until the date of first documented relapse, date of death from NPC or treatment-related toxicities, or date of last assessment, whichever came first. All eligible and treated patients were included in the analysis. | From date of attainment a complete response until the date of first documented relapse, date of death from NPC or treatment-related toxicities, or date of last assessment, whichever came first, assessed up to 5 years. | 
| Overall Survival | Overall survival was defined as the time from randomization until the date of death from any cause, or date of last assessment, whichever came first. All eligible and treated patients were included in the analysis. | From date of randomization until the date of death from any cause, or date of last assessment, whichever came first, assessed up to 5 years. | 
| Overall response rate | Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Overall response rate= complete response + partial response. Tumor measurements were performed using physical examination, computer tomography (CT) or Positron Emission Tomography-Computer Tomography (PET-CT) scans and Magnetic Resonance Imaging （MRI） scans, which were consist with baseline measurements methods. | every 6 weeks, up to 5 years. |