Online Adaptive Radiotherapy for Nasopharyngeal Carcinoma (OART)

Artificial Intelligence Empowered Online Adaptive Radiotherapy Versus Conventional Radiotherapy in Non-metastatic Nasopharyngeal Carcinoma: an Open-label, Non-inferiority, Multicentre, Randomised Phase 3 Trial

In this multicenter, prospective, randomized, controlled, non-inferiority Phase III clinical trial, treatment-naïve patients with nasopharyngeal carcinoma (NPC) without metastasis will be enrolled for curative radiotherapy. The participants will be randomly assigned to two groups. The experimental group will receive online adaptive radiotherapy (ART) during the radiotherapy process, with a smaller PTV margin, while the control group will use original treatment plan during full-course radiotherapy, with a PTV margin of 3 mm. The study aims to compare the survival, adverse events, and quality of survival between the two groups, with the primary endpoint being the locoregional recurrence-free survival rate. The main objective is to determine the role of online ART in nasopharyngeal carcinoma, elucidating its potential to alleviate radiation toxicity in patients while ensuring treatment efficacy.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Radiation: Intensity modulated radiation therapy (IMRT) with conventional planning target volume (PTV) margin and without online adaptive radiotherapy; Drug: Chemotherapy; Drug: Chemotherapy; Radiation: Intensity modulated radiation therapy (IMRT) with smaller planning target volume (PTV) margin and online adaptive radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 494
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yu-xian Yang, MD; Phone Number: +86 147 4892 2370; Email: yangyx1@sysucc.org.cn
• Study Contact Backup: Name: Guan-qun Zhou, PhD; Phone Number: +86 159 1437 2887; Email: zhougq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Yu-xian Yang; Phone Number: +86 147 4892 2370; Email: yangyx1@sysucc.org.cn
      • Contact: Guan-quan Zhou; Phone Number: +86 159 1437 2887; Email: zhougq@sysucc.org.cn
      • Principal Investigator: Ying Sun, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Newly diagnosed nasopharyngeal carcinoma confirmed by pathology, with a histological classification of non-keratinizing carcinoma (according to the World Health Organization, WHO), pathological classification.
2. No evidence of distant metastasis (M0).
3. Age between 18 and 70 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status score:0-1.
5. Undergoing radical intensity-modulated radiation therapy (IMRT).
6. No claustrophobia and able to remain in a fixed position for at least 30 minutes
7. Patients must be informed of the main content of this study, sign an informed consent form, and be willing and able to comply with the treatment, follow-up plan, laboratory tests, and other requirements specified in the study protocol.

Exclusion Criteria:

1. Histological types include squamous cell carcinoma or basal cell carcinoma.
2. Radiation therapy intended for palliative care.
3. History of malignant tumors, excluding adequately treated basal cell carcinoma, squamous cell carcinoma, and cervical intraepithelial neoplasia.
4. Pregnant or lactating women (women of childbearing age should undergo pregnancy testing; effective contraception should be emphasized during treatment.
5. Previous radical radiotherapy for nasopharyngeal cancer.
6. Primary and neck metastatic lesions treated with chemotherapy or surgery.
7. Presence of other serious underlying diseases that may pose a greater risk or affect compliance with the trial. Examples include unstable cardiac diseases requiring treatment, renal diseases, chronic hepatitis, poorly controlled diabetes (fasting blood glucose > 1.5×ULN), and psychiatric disorders.
8. Initial assessment of treatment efficacy more than 120 days after the end of radiotherapy.
9. Inability to undergo enhanced magnetic resonance imaging due to contrast agent allergies, claustrophobia.

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
Active Comparator: Conventional radiotherapy with conventional margins w or w/o chemotherapy; Complete the full course of radiotherapy using the original treatment plan. PTV margin: 3mm.	Radiation: Intensity modulated radiation therapy (IMRT) with conventional planning target volume (PTV) margin and without online adaptive radiotherapy; Radiation: Complete the full course of radiotherapy using the original treatment plan. Planning target volume (PTV) margin: 3mm; Drug: Chemotherapy; Chemotherapy: If given, platinum-based.; Drug: Chemotherapy; Chemotherapy: If given, platinum-based
Experimental: Radiotherapy with smaller margin and online adaptive radiotherapy w or w/o chemotherapy; Throughout the course of radiotherapy, the treatment plan is adjusted online based on the anatomical and dosimetric changes in the target volumes and organs at risk of the patients. PTV margin: smaller.	Drug: Chemotherapy; Chemotherapy: If given, platinum-based.; Drug: Chemotherapy; Chemotherapy: If given, platinum-based; Radiation: Intensity modulated radiation therapy (IMRT) with smaller planning target volume (PTV) margin and online adaptive radiotherapy; Radiation: During the course of radiotherapy, the treatment plan is adjusted online based on the anatomical and dosimetric changes in the target volumes and organs at risk of patients. planning target volume (PTV) margin: smaller.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional recurrence-free survival	locoregional progression free survival	3-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	overall survival	3-year
Distant metastasis free survival	Distant metastasis free survival	3-year
Rate of acute radiation-induced events according to Common Terminology Criteria for Adverse Events (CTCAE 5.0)	Acute radiation-induced events. The minimum and maximum values are 0 and 5 respectively. The higher scores mean a worse outcome.	3 months
Rate of late radiation-induced events according to Common Terminology Criteria for Adverse Events (CTCAE 5.0).	Late radiation-induced events. The minimum and maximum values are 0 and 5 respectively. The higher scores mean a worse outcome.	3-year
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 Version 1.0 (EORTC QLQ-HN35 V1.0)	The minimum and maximum values are 0 and 4 respectively. The higher scores mean a worse outcome.	From baseline to 3 years post-radiotherapy
and National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events Version 1.0 (NCI-PRO-CTCAE V1.0.)	The minimum and maximum values are 0 and 5 respectively. The higher scores mean a worse outcome.	From baseline to 3 years post-radiotherapy

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: December 27, 2023
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 17, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Nasopharyngeal Carcinoma; Online adaptive radiotherapy; Smaller PTV margin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: SL-B2023-685-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No