Proton vs Photon IMRT in Locally Advanced Nasopharyngeal Carcinoma: A Phase III Trial

NCT07340515 | Recruiting Phase 3 DMC

• 1 other identifier: 2025XH13
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, open-label, randomized Phase III trial evaluates intensity-modulated proton therapy (IMPT) versus intensity-modulated photon radiotherapy (IMRT) in patients with newly diagnosed, high-risk, locoregionally advanced nasopharyngeal carcinoma. All patients receive induction chemotherapy followed by concurrent chemoradiotherapy combined with immunotherapy and are randomized 1:1 to IMPT or IMRT during the concurrent treatment phase. The primary endpoints are the incidence of grade ≥3 acute treatment-related toxicities and the 3-year progression-free survival (PFS) rate. Secondary endpoints include overall survival, locoregional relapse-free survival, distant metastasis-free survival, objective response rate, late toxicities, and quality of life.

Conditions

Nasopharyngeal Carcinoma (NPC)

Keywords

Proton Therapy; IMPT; Intensity-Modulated Proton Therapy; Nasopharyngeal Carcinoma; Chemoradiotherapy

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-related grade ≥3 acute toxicities

  The proportion of patients who experience treatment-related grade ≥3 acute toxicities, defined as adverse events occurring from the start of radiotherapy to 90 days after completion of radiotherapy, assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and Radiation Therapy Oncology Group (RTOG) criteria. Ototoxicity (hearing loss or tinnitus), if present, will additionally be evaluated using the American Speech-Language-Hearing Association (ASHA, 1994) significant change criteria.

  From the start of radiotherapy to 90 days after completion of radiotherapy

• 3-year Progression-Free Survival (PFS) Rate

  Defined as the proportion of participants who remain alive and progression-free at 3 years after randomization, with progression-free survival events defined as disease progression or death from any cause, whichever occurs first.

  3 years

Secondary Outcomes (8)

• Overall Survival (OS)

  3 years

• Locoregional Recurrence-Free Survival (LRRFS)

  3 years

• Distant Metastasis-Free Survival (DMFS)

  3 years

• Objective Response Rate (ORR)

  2 weeks after induction chemotherapy and 3 months after completion of radiotherapy

• Incidence of Grade <3 Acute Treatment-Related Toxicities

  From the start of radiotherapy to 90 days after completion of radiotherapy

Study Arms (2)

IMPT Arm

EXPERIMENTAL

Participants assigned to this arm receive intensity-modulated proton therapy (IMPT). Radiotherapy is delivered according to the protocol-defined dose and fractionation schedule, using the same target delineation and prescription principles as IMRT, with dose converted to Gy(RBE) for proton therapy. IMPT treatment is administered concurrently with cisplatin-based chemotherapy and toripalimab as specified in the study protocol.

Radiation: Intensity-Modulated Proton Therapy (IMPT); Drug: Cisplatin; Biological: Toripalimab

IMRT Arm

ACTIVE COMPARATOR

Participants assigned to this arm receive intensity-modulated photon radiotherapy (IMRT) according to the protocol-defined dose and fractionation schedule. Radiotherapy is delivered to the primary tumor and involved lymph nodes following the target delineation and prescription principles specified in the study protocol. IMRT is administered concurrently with cisplatin-based chemotherapy and toripalimab, consistent with the protocol.

Radiation: Intensity-Modulated Radiation Therapy (IMRT); Drug: Cisplatin; Biological: Toripalimab

Interventions

Cisplatin DRUG

Cisplatin is administered during induction chemotherapy and concurrent chemoradiotherapy as specified in the protocol: 80 mg/m² IV on Day 1 every 21 days for 3 cycles during induction (GP regimen), and 100 mg/m² IV on Day 1 and Day 22 for 2 cycles during concurrent chemoradiotherapy.

IMPT Arm; IMRT Arm

Intensity-Modulated Proton Therapy (IMPT) RADIATION

Participants assigned to this arm receive intensity-modulated proton therapy (IMPT) according to the protocol-defined dose and fractionation schedule. Radiotherapy is delivered using the same target delineation and prescription principles as IMRT, with dose converted to Gy(RBE) for proton therapy. IMPT is administered concurrently with cisplatin-based chemotherapy and toripalimab as specified in the study protocol.

IMPT Arm

Intensity-Modulated Radiation Therapy (IMRT) RADIATION

Participants assigned to this arm receive intensity-modulated radiation therapy (IMRT) according to the protocol-defined dose and fractionation schedule. Radiotherapy is delivered to the primary tumor and involved lymph nodes following the target delineation and prescription principles specified in the study protocol. IMRT is administered concurrently with cisplatin-based chemotherapy and toripalimab, consistent with the protocol.

IMRT Arm

Toripalimab BIOLOGICAL

Toripalimab 240 mg is administered every 3 weeks during induction, concurrent chemoradiotherapy, and maintenance therapy for a total of 12 cycles unless disease progression or unacceptable toxicity occurs.

IMPT Arm; IMRT Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 70 years
• Histologically confirmed nasopharyngeal carcinoma (WHO type II or III)
• High-risk locoregionally advanced disease defined as clinical stage T4 or N3, M0, according to the AJCC staging system
• No prior anti-tumor therapy for nasopharyngeal carcinoma, including radiotherapy, chemotherapy, targeted therapy, or immunotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate organ function as defined in the study protocol
• Eligible to receive induction chemotherapy followed by concurrent chemoradiotherapy combined with immunotherapy as specified in the protocol
• Ability to understand and willingness to sign written informed consent

You may not qualify if:

• Evidence of distant metastasis (M1 disease)
• Prior radiotherapy, chemotherapy, targeted therapy, or immunotherapy for nasopharyngeal carcinoma
• Active autoimmune disease requiring systemic therapy
• Uncontrolled infection or severe comorbidities that may affect treatment tolerance
• Pregnancy or breastfeeding
• Known allergy, hypersensitivity, or contraindication to study medications as defined in the protocol
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation

Sponsors & Collaborators

• Man Hu: lead
• Shandong Cancer Hospital and Institute: collaborator

Study Sites (1)

Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences

Jinan, Shandong, 250117, China

RECRUITING

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin; toripalimab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Model Details: Participants are randomized in a 1:1 ratio to receive intensity-modulated proton therapy (IMPT) or intensity-modulated photon radiotherapy (IMRT) using a parallel-group design.

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: January 14, 2026
• Study Start: December 15, 2025
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2031
• Last Updated: January 14, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)