Proton vs Photon IMRT in Locally Advanced Nasopharyngeal Carcinoma: A Phase III Trial
A Prospective, Randomized, Open-Label, Multicenter Phase III Clinical Study Comparing Intensity-Modulated Proton Therapy and Intensity-Modulated Photon Radiotherapy in Locally Advanced Nasopharyngeal Carcinoma
Man Hu
300 participants
Dec 15, 2025
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria8
- 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
Exclusion Criteria7
- 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
Interventions
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.
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.
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.
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.
Locations(1)
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NCT07340515