Clinical trial NCT06529562: Surgery Plus Reduced Target Chemoradiotherapy vs Surgery Plus Reduced Dose Chemoradiotherapy for Newly Diagnosed Operable Nasopharyngeal Carcinoma.
Official title: Surgery Plus Reduced Target Chemoradiotherapy Versus Surgery Plus Reduced Dose Chemoradiotherapy for Newly Diagnosed Operable Nasopharyngeal Carcinoma : a Prospective, Multicenter, Radomized Control Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nasopharyngeal Carcinoma
Keywords: Surgery
Target-Reduction Chemoradiotherapy
Dose-Reduction Chemoradiotherapy
Locally Resectable Nasopharyngeal Carcinoma
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Fifth Affiliated Hospital, Sun Yat-Sen University
name: Sun Yat-sen University
name: Fifth Affiliated Hospital of Guangzhou Medical University
name: Huazhong University of Science and Technology Union Hospital (Nanshan Hospital)
name: The First Affiliated Hospital of University of South China
name: People's Hospital of Guangxi Zhuang Autonomous Region
name: Nanchang City First Hospital
First posted: 2024-07-31
Enrollment: 384
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare surgery plus reduced target chemoradiotherapy with surgery plus reduced dose chemoradiotherapy in newly diagnosed operable Nasopharyngeal Carcinoma.The main questions it aims to answer are:whether endoscopic surgery combined with reduced dose chemoradiotherapy vs surgery plus target reduction chemoradiotherapy can bring substantial survival benefits, lower toxicity, and shorter treatment cycle for patients with operable nasopharyngeal carcinoma .

Detailed description: Currently, the treatment of newly diagnosed non-metastatic nasopharyngeal carcinoma with intensity modulated radiotherapy as the core and chemotherapy with platinum-containing drugs has achieved good therapeutic outcomes. However, the toxicity and side effects caused by local radiotherapy greatly affect the quality of life of patients with nasopharyngeal carcinoma during treatment. In order to find a more "high-efficiency and low-toxicity" nasopharyngeal cancer treatment mode, combined with minimally invasive surgery for radical tumor treatment and radiotherapy and chemotherapy to eliminate potential micro-metastatic lesions,, Our team has previously carried out "prospective clinical trial of newly diagnosed operable nasopharyngeal carcinoma surgery combined with reduced target chemoradiotherapy versus conventional chemoradiotherapy", It has been prelim natively confirmed that gross tumor volume(GTV) and clinical tumor volume (CTV1) high-risk infiltrating area need not be recharacterized after the combined nasopharyngeal or non-combined retropharyngeal surgery and radical resection of cervical lesions. Only low risk infiltrating area (CTV2) was delineated and preventive irradiation of 54 Gy/33 times /45 days was administered, combined with induction or concurrent chemotherapy. Preliminary study results showed that it could further reduce the local recurrence of tumors and the overall curative effect while reducing the toxic side effects of treatment and achieve the therapeutic effect of increased efficacy and reduced toxicity.

Although compared to the conventional radiotherapy dose of 70Gy, postoperative reduced target radiotherapy has achieved a significant reduction in radiotherapy dose while ensuring tumor control, However, we are concerned that nearly 40% of patients still have ≥ grade 3 dry mouth, mucosal ulcer, mouth difficulty and dysphagia during or after treatment. Therefore, for newly diagnosed patients with surgically resectable nasopharyngeal carcinoma, we plan to conduct a prospective clinical trial comparing the survival prognosis and toxic side effects of newly diagnosed surgery combined with reduced dose radiotherapy compared with conventional reduced target radiotherapy combined with concurrent chemotherapy. To explore whether this treatment model can bring comparable survival benefits, lower toxic side effects and shorter treatment cycles for patients.

According to our team's previous research results and literature data, we designed the following scheme: patients with operable nasopharyngeal carcinoma were assigned to the control group and the experimental group. Control group: nasopharyngeal combined with or without combined retropharyngeal and neck lesions radical surgery, postoperative routine target reduction chemoradiotherapy at the same period. Experimental group: Patients underwent radical surgery with or without nasopharynx combined with retropharyngeal and cervical lesions, followed by concurrent low-dose radiotherapy and chemotherapy.

Eligibility criteria: 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, 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) and tumor diameter ≤1.5cm. Resectable retropharyngeal lymph nodes were defined as; The diameter was ≤ 1.5cm, the tissue space was intact, and there was no obvious extranodal invasion; The resectable cervical lymph nodes were defined as ≤ 3cm in diameter, located above the lower edge of the cricoid cartilage, with moderate mobility and no obvious extranodal invasion. Clinical stage: T1-3N1-2M0, T2-3N0M0 (Stage II-III) according to AJCC 8th staging edition.
* 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 organ dysfunction or physical disorder which could not tolerate surgery or radiotherapy or chemotherapy.
* Retropharyngeal lymph node diameter\>1.5cm, or extranodal invasion, such as invasion of internal carotid artery, muscle, or extensive extracapsular dissemination.
* Cervical lymph node diameter\>3cm, or in the area below the lower margin of the cricoid cartilage, or with extranodal invasion, such as invasion of the internal carotid artery, skin, muscle, mediastinal structure, prevertebral fascia or cervical spine, or extensive extra-capsular spread, subcutaneous metastasis, etc.
* 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.

Primary outcomes:
measure: Locoregional Recurrence-Free Survival Time (LRRFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
measure: Incidence of Treatment-Related Adverse Events
timeFrame: 1 years
measure: Distant Metastasis-Free Survival (DMFS)
timeFrame: 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire (QLQ)-C30 (V3.0)
timeFrame: 3 years
measure: Score of survival quality according to the EORTC Quality of Life Questionnaire Head and Neck (The QLQ-H&N35)
timeFrame: 3 years
measure: Progression-Free Survival (PFS)
timeFrame: 3 years
Other outcomes:
Locations:
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: SUN yet-sen University
name: Ming-Yuan Chen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: