Carbon-Ion Radiotherapy Plus Camrelizumab for Locally Recurrent Nasopharyngeal Carcinoma

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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A Phase 2 Randomized Clinical Trial to Examine the Efficacy of Carbon-Ion Radiotherapy Plus Camrelizumab As Salvage Treatment for Locally Recurrent Nasopharyngeal Carcinoma

Conditions
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Nasopharyngeal Carcinoma

Intervention / Treatment
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* Drug: Induction chemotherapy
* Radiation: Carbon-ion radiotherapy
* Drug: Camrelizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm-C<br>Patients will receive induction chemotherapy followed by carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE). | Drug: Induction chemotherapy<br>* Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.<br>Radiation: Carbon-ion radiotherapy<br>* Accelerated carbon-ion beam with pencil beam scanning technique.<br>|
| Experimental: Arm-CC<br>Patients will receive induction chemotherapy followed by carbon-ion radiotherapy and camrelizumab. In details, patients will receive carbon-ion radiotherapy with a dose of 63 GyE in 21 fractions (the fraction size is 3 GyE); in addition, patients will also receive camrelizumab of 200 mg (IV.), every 2 weeks, started with carbon-ion radiotherapy for a maximal period of 1 year. | Drug: Induction chemotherapy<br>* Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.<br>Radiation: Carbon-ion radiotherapy<br>* Accelerated carbon-ion beam with pencil beam scanning technique.<br>Drug: Camrelizumab<br>* An anti-PD-1 antibody.<br>* Other names: SHR-1210;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Duration from randomization to documented disease recurrence or death from any cause, whichever occurs first. | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Duration from randomization to death from any cause. | 2-year | 
| Local progression-free survival | Duration from randomization to documented local recurrence or death from any cause, whichever occurs first. | 2-year | 
| Regional progression-free survival | Duration from randomization to documented regional recurrence or death from any cause, whichever occurs first. | 2-year | 
| Distant metastasis-free survival | Duration from randomization to documented distant metastasis or death from any cause, whichever occurs first. | 2-year | 
| Number of participants with adverse events | Incidence of adverse events | 2-year |