Hypofractionated Versus Conventionally Fractionated Radiotherapy for Initial Distant Metastases Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Radiotherapy is an important treatment for initial distant metastases nasopharyngeal carcinoma. Total dose and fraction size are important prognostic factors for survival, although to our knowledge the optimal model has not been well determined to date. The purpose of this clinical trial is to investigate the optimal radiation dose to investigate the feasibility of decreasing the total dose and increasing the fraction size with the objective of achieving a better balance between local control and severe late complications. for initial distant metastases nasopharyngeal carcinoma with definitive radiotherapy.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine if hypofractionated with a smaller total dose radiation is not inferior to standard-dose radiation in progression-free survival for initial distant metastases nasopharyngeal carcinoma . SECONDARY OBJECTIVES: I. To evaluate if hypofractionated with a low total dose radiation is not inferior to standard-dose radiation in overall survival and locoregional failure-free survival for initial distant metastases nasopharyngeal carcinoma II. To evaluate if hypofractionated with a low total dose radiation with chemotherapy decrease treatment-related toxicities OUTLINE: Patients are randomized to one of the two treatment arms ARM 1: Patients receive hypofractionated with a low total dose radiation with induced chemotherapy and adjuvant chemotherapy.Hypofractionated dose IMRT: GTVnx 60Gy, GTVnd 60Gy, PTV1 50Gy and PTV2 45Gy in 25 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. ARM 2: Patients receive standard-dose radiation with concurrent chemotherapy. Standard-dose IMRT: GTVnx 69.69Gy, GTVnd 60-68Gy, PTV1 59.4Gy and PTV2 54Gy in 33 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 75mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After completion of study therapy, patients are followed up every 3-4 months for 2 years, then every 6 months for 3 years.

Official Title
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A Multicenter, Prospective, Randomized, Phase II Trial Evaluating Hypofractionated Versus Conventionally Fractionated Radiotherapy for Initial Distant Metastases Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Radiation: Hypofraction radiation
* Radiation: Standard dose IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly histologically confirmed non-keratinizing (according to WHO histologically type) Tumor staged as any T or any N with M (according to the 8th AJCC edition). No pregnant female Age between 18-70 Normal complete blood count level (hemoglobin >10 g/dL, white blood cells ≥4000/μL, platelets ≥100 000/μL) Normal hepatic functions (serum total bilirubin ≤1.6 mg/dL, serum transminase < 2.5 times higher than upper limit) Normal renal function (serum creatinine ≤1.5 mg/dL, creatinine clearance ≥60 mL/min) Karnofsky performance status (KPS) score of at least 70 Without radiotherapy or chemotherapy Patients must give signed informed consent Exclusion Criteria: Other or mixed pathological type age > 70 years or <18 years Prior chemotherapy, radiation, surgical resection or target therapy of the primary tumor; Significant medical or psychiatric illnesses that in the physician's judgment (uncontrolled coronary heart disease, cardiomyopathy and/or heart failure requiring hospitalization. Uncontrolled hypertension or history of myocardial infarction within one year. Uncontrolled diabetes mellitus. Acute bacterial or fungal infection requiring intravenous antibiotics; Refused to sign informed consent form Concurrent pregnancy or lactation History of a second malignancy other than nasopharyngeal carcinoma

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypofractionated dose IMRT<br>Patients receive hypofractionated with a low total dose radiation with induced chemotherapy and adjuvant chemotherapy. | Radiation: Hypofraction radiation<br>* Hypofractionated dose IMRT: GTVnx 60Gy, GTVnd 60Gy, PTV1 50Gy and PTV2 45Gy in 25 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.<br>|
| Experimental: Standard-dose IMRT<br>Patients receive standard-dose radiation therapy with induced chemotherapy and adjuvant chemotherapy.. | Radiation: Standard dose IMRT<br>* Standard dose IMRT: GTVnx 69.69Gy, GTVnd 60-68Gy, PTV1 54.9Gy and PTV2 54Gy in 33 fractions, 5 days/week. Induced chemotherapy: Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles. After radiation, patients receive adjuvant chemotherapy Paclitaxel 135mg/m2 D1+Cisplatin 80mg/m2 D1(or D1-3), 3-week chemotherapy for 3 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | The time from the first day of therapy to locoregional relapse, distant relapse or tumor-related death | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The time from the first day of therapy to death or last follow-up. | 2 years | 
| Locoregional relapse-free survival | The time from the first day of treatment to the time of first locoregional relapse | 2 years | 
| Distant metastasis-free survival | The time from the first day of treatment to the time of first distant metastasis | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypofractionated Radiation, initial distant metastases, nasopharyngeal carcinoma