The purpose of this trial is to examine the role of camrezlizumab in addition to carbon-ion radiotherapy (CIRT) for patients with locally recurrent nasopharyngeal carcinoma. According to the plan, a total of 146 patients will be recruited and randomized into: 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group).

Treatment for locally recurrent nasopharyngeal carcinoma (LR-NPC) is challenging. Carbon-ion radiotherapy appeared to be an effective treatment for this group of patients, and has substantially improved the 2-year overall survival (OS) to approximately 85%, compared to photon-based intensity-modulated radiotherapy. However, a group of the patients may still develop disease progression after CIRT, and the 2-year progression-free survival (PFS) was approximately 45%-50%. Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been demonstrated that it is effective in the recurrent/metastatic nasopharyngeal carcinoma; however, the role of camrelizumab in concurrence with radiotherapy, especially CIRT, for LR-NPC is not clear. The purpose of this phase 2 clinical trial is to compare the efficacy of CIRT plus camrelizumab and CIRT alone in the treatment of LR-NPC. Eligible participants will be randomized (1:1) to 1) CIRT alone group (control group); 2) CIRT plus camrelizumab group (experimental group). The primary endpoint is progression-free survival. Secondary endpoints include overall survival (OS), local progression-free survival (LPFS), regional progression-free survival (RPFS), and distant metastasis-free survival (DMFS) and toxicities. All efficacy analyses are conducted in the intention-to-treat population, and the safety population include only patients who receive their randomly assigned treatment.

Inclusion Criteria:

• Completed a definitive course of intensity-modulated photon radiation therapy (IMRT) to a total dose of ≥ 66 Gy
• Recurrence at nasopharynx diagnosed more than 6 months after the initial course of IMRT
• Patients with neck lymphadenopathy should receive neck dissection before randomization
• With measurable lesion on contrast MR scan
• Age ≥ 18 and < 70 years of age
• ECOG score: 0-1
• Leucocyte count ≥ 4000/µL, neutrocyte count ≥ 2000/µL, platelet count ≥ 100000/µL, hemoglobin ≥ 90g/L
• Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) < 1.5×upper limit of normal (ULN), alkaline phosphatase < 2.5×ULN, bilirubin ≤ ULN, serum creatinine ≤ ULN, creatinine clearance ≥ 60ml/min
• Willing to accept adequate contraception
• Ability to understand the nature of the clinical trial and sign the written informed consent

Exclusion Criteria:

• Presence of distant metastasis
• Previously received radioactive particle implantation
• Prior malignancy within 5 years before randomization, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer
• Patients who received local (such as surgery and cryotherapy) or systemic treatment, except for induction chemotherapy after diagnosis of recurrence
• With uncontrolled active infection
• With pneumonia
• With autoimmune disease
• With a known history of testing positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• Hepatitis B virus (HBV) DNA ≥ 500IU/mL for patients with positive HBV surface antigen, positive hepatitis C virus RNA for patients with positive HCV antigen
• Previously treated by immune checkpoint inhibitors
• Medical conditions requiring treatment of antibiotics and/or corticosteroid
• Treated with ≥ 5 days antibiotics one month before start of immunotherapy
• With known allergy to any of the study drugs
• Pregnant or lactating women
• Any severe intercurrent disease that may interfere with the current study

Data on participants' clinical features, treatment modalities, survivals and toxicity profile will be shared upon reasonable request. Detailed study protocol should be emailed along with the request of the data. We may carefully review the study protocol, and data will only be shared with well-designed studies.

Within 3 years after publication of the study.

Data mentioned in the plan description and relevant supporting files will be shared with radiation oncologist who are interested in conducting pooled analysis comparing carbon-ion radiotherapy with other treatment modalities (such as other radiation technique and systemic therapy) for patients with recurrent nasopharyngeal carcinoma. The IPD will only be shared after the study protocol is reviewed and approved by the principle investigator.