Surgery Plus Target-reduction Chemoradiotherapy vs Regular Chemoradiotherapy for Newly Diagnosed Resectable Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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Through a prospective clinical trial, we intend to combine surgery, induction chemotherapy, target-reduction intensity-modulated radiotherapy and concurrent chemotherapy as an experimental treatment for patients with newly diagnosed resectable nasopharyngeal carcinoma to illuminate whether combined surgery could bring patients better local-regional control and lower adverse reactions.

Official Title
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Multicenter Randomized Controlled Trial of Surgery Plus Target-reduction Chemoradiotherapy vs Regular Chemoradiotherapy for Newly Diagnosed Resectable Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Cisplatin
* Radiation: regular intensity-modulated radiotherapy
* Procedure: surgery
* Radiation: Target-reduction intensity-modulated radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Performance Status Score 0-1 points. Non-keratinized carcinoma of the nasopharynx (differentiated or undifferentiated, i.e., WHO type II or III) confirmed histologically and/or cytologically. Patients with primary nasopharyngeal lesions evaluated as surgically resectable before chemotherapy, including T1 (tumor limited to nasopharynx), T2 (tumor limited to the surface of parapharyngeal space) and T3 (tumor limited to the bottom wall of sphenoid sinus or pterygoid process). Clinical stage: T1-3N1-3M0, T2-3N0M0 (Stage II-IVA) according to AJCC v8. Patients with cervical lymph nodes evaluated as surgically resectable before chemotherapy, including cervical lymph nodes with no invasion (encasement) of the common or ICA, the epidermis, mediastinal structures, prevertebral fascia, or cervical vertebrae. Patients with retropharyngeal lymph nodes evaluated as surgically resectable before chemotherapy, including simple RPLNs with intact capsule or RPLNs ≤ 1.5cm with mouth opening range > 4cm. Adequate organ function: WBC ≥ 4×10^9 /L, NEUT ≥ 2×10^6 /L, HGB ≥ 9 g/dL, PLT count ≥ 100×10^9/L, TBIL ≤1.5 ULN (TBIL ≤3 ULN for patients with Gilbert Disease), ALT ≤3 ULN, AST ≤3 ULN, ALP ≤3 ULN, ALB ≥ 3 g/dL, INR or APTT≤1.5 ULN, Scr ≤1.5 ULN or Ccr ≥ 60 mL/min. Informed Concent signed with willingness to obey the follow-up, treatment, examination and any other programs according to the research protocol. Exclusion Criteria: Diagnosed as recurrent or distant metastatic nasopharyngeal carcinoma or together with any other malignancy. Suffering severe cardiopathy or pulmonary dysfunction with cardiac or pulmonary function no more than grade 3. Extensive recurrent primary tumour beyond the resectable area such as extensive invasion of the skull base or a distance from the tumour margins to the internal carotid artery of less than 0·5 cm. Retropharyngeal lymph node involved or adjacent to primary nasopharyngeal lesions (less than 0·5 cm). Unable to cooperate with regular follow-up due to psychological, social, domestic or geological reasons. During pregnancy or lactation. Other patients that the chief physician considered as illegal for this trial.

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: Surgery Plus Target-reduction Chemoradiotherapy<br>Surgery: Endoscopic nasopharyngectomy: Radical resection of primary lesion using nasal endoscopy. Retropharyngeal lymphadenectomy: Radical retropharyngeal LNs resection using nasal endoscopy or da Vinci robotics. Neck lymph node dissection: Selective neck dissection of the region where the positive lymph nodes are located. Induction Chemotherapy for stage III-IVa: Gemcitabine, 1000 mg/m2, Day 1 and Day 8, Q3W, 3 cycles Cisplatin, 80 mg/m2, Day 1, Q3W, 3 cycles Intensity-modulated Radiotherapy with GTV and CTV1 reduction: CTV2 : 54.12Gy/33Fr/1.64Gy Concurrent Chemotherapy: Cisplatin, 100 mg/m2, intravenously, Day 1, Q3W during radiotherapy | Drug: Gemcitabine<br>* for induction chemotherapy<br>Drug: Cisplatin<br>* for induction and concurrent chemotherapy<br>Procedure: surgery<br>* in experimental arm<br>* Other names: Neck lymph node dissection;Radiation: Target-reduction intensity-modulated radiotherapy<br>* in experimental arm<br>|
| Active Comparator: Regular Chemoradiotherapy<br>Induction Chemotherapy for stage III-IVa: Gemcitabine, 1000 mg/m2, intravenously within 30min, Day 1 and Day 8, Q3W, 3 cycles Cisplatin, 80 mg/m2, intravenously, Day 1, Q3W, 3 cycles Intensity-modulated Radiotherapy: GTVnx (nasopharyngeal lesions): 69.96Gy/33Fr/2.12Gy GTVrnd (retropharyngeal lymph nodes): 69.96Gy/33Fr/2.12Gy GTVnd: 69.96Gy/33Fr/2.12Gy CTV1: 60.60Gy/33Fr/1.82Gy CTV2: 54.12Gy/33Fr/1.64Gy Concurrent Chemotherapy: Cisplatin, 100 mg/m2, intravenously, Day 1, Q3W during radiotherapy | Drug: Gemcitabine<br>* for induction chemotherapy<br>Drug: Cisplatin<br>* for induction and concurrent chemotherapy<br>Radiation: regular intensity-modulated radiotherapy<br>* in active comparator arm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local Regional Relapse-Free Survival (LRRFS) | The LRRFS is evaluated and calculated from the date of random assignment until the day of first local regional relapse or until the date of the last follow-up visit. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | The OS was defined as the duration from the date of random assignment to the date of death from any cause or censored at the date of the last follow-up. | 3 years | 
| Progress-free survival (PFS) | Progress-free survival is calculated from the date of randomization to the date of the first progression of any site or death or censored at the date of the last follow-up. | 3 years | 
| Distant Metastasis-Free Survival (DMFS) | The DMFS is evaluated and calculated from the date of random assignment until the day of first distant metastases or until the date of the last follow-up visit. | 3 years | 
| Regional Relapse-Free Survival (RRFS) | The RRFS was defined as the duration from the date of random assignment to the date of regional relapse or censored at the date of the last follow-up. | 3 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. | 3 years | 
| Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) | Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35) before treatment, during treatment, after treatment. | 3 years | 
| Incidence of treatment related acute complications | The proportion of patients with treatment related acute complications according to NCI-CTC5.0 criteria and RTOG criteria. | 1 years | 
| Incidence of treatment related late complications | The proportion of patients with treatment related late complications according to NCI-CTC5.0 criteria and RTOG criteria. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Surgery, Target-reduction Chemoradiotherapy, Locally Resectable Nasopharyngeal Carcinoma