Phase 3 Trial Comparing IMRT or IMPT Plus CIRT for Patients With NPC

Phase 3 Trial Comparing IMRT or IMPT Plus CIRT for Patients With NPC

The goal of this phase 3 non-inferiority trial is to compare the efficacy and toxicity of proton or photon radiation therapy plus carbon ion radiation therapy for newly diagnosed nasopharyngeal carcinoma. The main question it aims to answer is that if proton radiation therapy plus carbon ion radiation therapy is non-inferior to photon radiation therapy plus carbon ion radiation therapy in terms of therapeutic efficacy. Participants will be randomized to receive either proton radiation therapy (arm 1) or photon radiation therapy (arm 2), in addition to carbon ion radiation therapy (for both arms).

This is a phase 3 randomized non-inferiority trial. The primary objective of the trial is to compare progression-free survival between proton plus carbon ion radiation therapy (arm 1) and photon plus carbon ion radiation therapy (arm 2) for patients with newly diagnosed nasopharyngeal carcinoma (NPC). The secondary objectives includes overall survival, locoregional progression-free survival, distant metastasis-free survival, physician-graded toxicities according to the CTCAE, and patients-reported outcomes. This study adopts a web-based central randomization system. The randomization method uses minimization, with two balancing factors: Stage (AJCC Staging System, 9th edition): Stage I vs. Stages II/III; Response to induction chemotherapy: No induction chemotherapy vs. sensitive (CR + PR) vs. resistant (SD + PD). Eligible patients will be randomized in a 1:1 ratio into either the experimental group or the control group. This is an open-label study, meaning both patients and investigators are aware of the treatment allocation.

Participants randomized to arm 1 will receive proton therapy with a dose of 56 GyRBE in 28 fractions, in addition to a boost delivered using carbon ion radiation therapy with a dose of 17.5 GyRBE in 5 fractions. Participants randomized to arm 2 will receive photon therapy with a dose of 56 Gy in 28 fractions, plus carbon ion radiation therapy with a dose of 17.5 GyRBE in 5 fractions. The treatment response will be evaluated according to the RECIST criteria.

Induction chemotherapy and concurrent chemotherapy will be prescribed according to disease stage.

Inclusion criteria:

• Willingness to sign the written informed consent.
• Pathologically confirmed Nasopharyngeal carcinoma.
• Patients with any stage of disease except distant metastasis.
• Age: ≥ 18 and ≤ 70 years old.
• Eastern Cooperative Oncology Group score: 0-1.
• Adequate laboratory test results.
• Willingness to accept adequate contraception.

Exclusion criteria:

• Presence of distant metastasis.
• Previous radiotherapy to head and neck region.
• Previous surgery (except for biopsy) for the primary lesion or cervical lymph nodes.
• History of malignant tumor within the past 5 years.
• Presence of multiple primary tumors.
• Presence of diseases that may interfere with the evaluation of study endpoints.
• Presence of severe major organ dysfunction.
• Mental illness that may affect the understanding of informed consent.