Reduced-dose Versus Standard Dose Radiotherapy for Nasopharyngeal Carcinomain

Phase III Randomized Non-inferiority Trial of Reduced-dose Versus Standard Dose Radiotherapy for Stage II-III Nasopharyngeal Carcinoma Which Have Favorable Response After Induction Chemotherapy

To study the 2-year PFS (progression-free survival) of patients with stage II-III nasopharyngeal carcinoma treated with induction chemotherapy followed by two different doses of intensity modulated radiation therapy plus concurrent cisplatin chemotherapy

Study Overview

• Status: Active, not recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: IMRT; Drug: induction chemotherapy; Drug: cisplatin concurrent chemotherapy

Detailed Description

To explore the 2 year PFS of patients with stageII-III nasopharyngeal carcinoma treated with induction chemotherapy followed by reduced-dose radiotherapy and cisplatin versus standard dose radiotherapy plus cisplatin concurrent chemotherapy. The enrolled patients will receive 2 cycles of cisplatin-based induction chemotherapy, if radiographic CR/PR and EBV DNA=0 after induction chemotherapy, the patients will be randomised assigned to received 60 Gy IMRT combined with 2 cycles of cisplatin concurrent chemotherapy or 70Gy IMRT combined with 3 cycles of cisplatin concurrent chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 452
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen Universitty Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients newly diagnosed with histologically confirmed non-keratinizing NPC (WHO type II or III).
2. Stage II-III（8thAJCC/UICC staging system)
3. Aged 18-70 years
4. ECOG = 0-1
5. HGB≥90 g/L，WBC≥4×109 /L，PLT≥100×109 /L
6. ALT,AST<1.5 x ULN；TBIL<1.5×ULN
7. CCR≥60ml/min or Cr<1.5×ULN
8. CR/PR and EBVDNA undetectable after induction chemotherapy
9. Signed informed consent

Exclusion Criteria:

1. WHO Type keratinizing squamous cell carcinoma or basaloid squamous cell carcinoma
2. Age <18 or >70years
3. Treatment with palliative intent
4. Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer
5. Pregnancy or lactation
6. History of previous radiotherapy (except for non-melanomatous skin cancers outside intended RT treatment volume)
7. Prior chemotherapy or surgery (except diagnostic) to primary tumor or nodes
8. Any severe intercurrent disease, which may bring unacceptable risk or affect the compliance of the trial, for example, unstable cardiac disease requiring treatment, renal disease, chronic hepatitis, diabetes with poor control (fasting plasma glucose >1.5×ULN), and emotional disturbance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Reduced-dose group; After 2 cycles of induction chemotherapy, patients with favorable response undergo low-dose (60Gy) intensity-modulated radiotherapy (IMRT) 5 days per week for approximately 6 weeks (30 fractions). Patients also receive concurrent cisplatin once every three weeks for 2 cycles.	Radiation: IMRT; Patients in experimental group received reduced dose IMRT; Drug: induction chemotherapy; cisplatin-based induction chemotherapy for two cycles; Drug: cisplatin concurrent chemotherapy; cisplatin 100mg/m2, for two(60Gy) or three cycles(70Gy)
Active Comparator: Standard dose group; After 2 cycles of induction chemotherapy, patients with favorable response undergo standard-dose (70Gy) intensity modulated radiotherapy (IMRT) 5 days per week for approximately 7 weeks (33 fractions). Patients also receive concurrent cisplatin once every three weeks for 3 cycles.	Radiation: IMRT; Patients in experimental group received reduced dose IMRT; Drug: induction chemotherapy; cisplatin-based induction chemotherapy for two cycles; Drug: cisplatin concurrent chemotherapy; cisplatin 100mg/m2, for two(60Gy) or three cycles(70Gy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS (progression-free survival)	Defined as the time from randomization to documented disease recurrence (either distant metastasis or locoregional disease recurrence) or death from any cause, whichever occurred first.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival(OS)	Defined as the time from randomization to death from any cause	2 year
Locoregional relapse-free survival(LRFS)	Defined as the time from randomization to the first local or regional recurrence, or death from any cause. follow-up visit.	2 year
Distant metastasis-free survival(DMFS)	Defined as the time from randomization to the first distant metastasis or death from any cause.	2 year
Overall response rate	Tumour response rate was classified according to RECIST, version 1.1	3 months
Incidence rate of adverse events (AEs)	Analysis of acute and late adverse events (AEs) are evaluated. Numbers of patients of treatment-related adverse events(acute toxicity) as assessed by CTCAE v5.0.Numbers of patients of late radiation toxicities were assessed using the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer late radiation morbidity scoring scheme.	2 year
Change of QoL	QoL scores were assessed for each scale by using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTCQLQ-C30) before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy	1 year
Change of EORTC quality of life questionnaire(QLQ) Head and Neck score	QoL scores were assessed by using EORTC quality of life questionnaire(QLQ) Head and Neck. The QLQ-H&N35 is composed of seven multi-item symptom scales (pain, swallowing, sensation, speech, eating from a social,perspective, social interactions, and sexuality) and 11 single-item symptom scales (teeth, opening mouth,dry mouth, sticky saliva,coughing, felt ill, pain medication use, nutritional supplementation, feeding tube requirement, weight loss, and weight gain). All of the scales and items ranged in score from 0 to 100. A high score for a functional or global QoL scale represents a relatively high/healthy level of functional or global QoL, whereas a high score for a symptom scale or item represents a high number of symptoms or problems.All of the scores mentioned above were assessed at the below time point:before induction chemotherapy, before radiotherapy, at the end of radiotherapy, at 3 months after radiotherapy, at 6 months after radiotherapy and 12 months after radiotherapy	1 year

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Study Chair: Hai Qiang Mai, Dr, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Estimated): October 29, 2026
• Study Completion (Estimated): October 29, 2029

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 18, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: radiotherapy; induction chemotherapy; Nasopharyngeal Carcinoma
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Carcinoma; Antineoplastic Agents; Cisplatin
• Other Study ID Numbers: 2022-FXY-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No