Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma

Predictive-Model Based Individualized Carbon-Ion Radiotherapy for Patients With Locally Recurrent Nasopharyngeal Carcinoma: A Phase 2 Randomized Trial

This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized carbon-ion radiotherapy (CIRT). For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups.

This is a randomized phase 2 trial with 2 groups (control group vs experimental group). Patients with locally recurrent nasopharyngeal carcinoma (LR-NPC) assigned to the control group will receive standardized CIRT with a dose of 63 gray equivalent (GyE) in 21 fractions (fx). This regimen was obtained from our previous phase 1 (dose escalation) study. For patients assigned to the experimental group, a predictive model will be used to predict the chance of developing mucosal necrosis after salvage carbon-ion radiotherapy, and individualized dose prescription will be given. A dose of 60 GyE/20 fx, 63 GyE/21 fx and 66 GyE/22 fx will be given to patients with high, moderate and low risk of developing mucosal necrosis, respectively. The primary endpoint of the study is to compare the 2-year progression-free survival (PFS) between 2 groups. The secondary endpoints include 2-year overall survival (OS), local progression-free survival, regional progression-free survival, distant metastasis-free survival, toxicities and quality of life.

Inclusion Criteria:

• Aged between 17-70 years.
• Pathologically diagnosed as WHO type 2/3 nasopharyngeal carcinoma.
• Failed previous definitive radiotherapy at least 6 months ago.
• Only had 1 previous course of radiotherapy.
• Eastern Cooperative Oncology Group score: 0-1.
• Adequate laboratory values within 30 dyas of enrollment to study defined as follows: 1) neutrophil > 2000/mm^3; 2) platelet > 100,000/mm^3; 3) total bilirubin < 1.5mg/dl; 4) alanine aminotransferase/aspartate aminotransferase < 1.5 upper limit of normal; 5) SCr < 1.5mg/dl; creatinine clearance rate > 60ml/min.
• Willing to accept adequate contraception for women with childbearing potential.
• Willing to sign the written informed consent; Informed consent must be signed before the enrollment in the trial.

Exclusion Criteria:

• Presence of distant metastasis.
• Without measurable lesion.
• Previous history of malignant tumor (within 5 years) or simultaneous existence of multiple primary tumors.
• Accompanied with severe major organ dysfunction.
• Presence of mental disease that may influence the understanding of informed consent.