carbon-ion radiotherapy plus camrelizumab for locally recurrent nasopharyngeal carcinoma

Conditions: Nasopharyngeal Carcinoma

Summary: 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.

Eligibility criteria:
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