Carbon-Ion Radiotherapy Plus Camrelizumab for Locally Recurrent Nasopharyngeal Carcinoma

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

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).

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Induction chemotherapy; Radiation: Carbon-ion radiotherapy; Drug: Camrelizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 146
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jiyi Hu, MD, PhD; Phone Number: 53513 +8602138296666; Email: jiyi.hu@sphic.org.cn
• Study Contact Backup: Name: Lin Kong, MD; Phone Number: 53516 +8602138296666; Email: konglin@sphic.org.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 201315
      • Recruiting
      • Shanghai Proton and Heavy Ion Center
      • Contact: Jiyi Hu, MD, PhD; Phone Number: 53513 +8602138296666; Email: jiyi.hu@sphic.org.cn
      • Contact: Lin Kong, MD; Phone Number: 53516 +8602138296666; Email: konglin@sphic.org.cn
      • Sub-Investigator: Lin Kong, MD
      • Sub-Investigator: Jiyi Hu, MD, PhD
      • Sub-Investigator: Weixu Hu, MD
      • Sub-Investigator: Jing Yang, MD
      • Sub-Investigator: Jing Gao, MD
      • Sub-Investigator: Xianxin Qiu, MD
      • Sub-Investigator: Qingting Huang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm-C; 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; Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.; Radiation: Carbon-ion radiotherapy; Accelerated carbon-ion beam with pencil beam scanning technique.
EXPERIMENTAL: Arm-CC; 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; Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.; Radiation: Carbon-ion radiotherapy; Accelerated carbon-ion beam with pencil beam scanning technique.; Drug: Camrelizumab; An anti-PD-1 antibody.; Other Names: SHR-1210

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shanghai Proton and Heavy Ion Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 19, 2021
• Primary Completion (ANTICIPATED): December 20, 2025
• Study Completion (ANTICIPATED): December 20, 2025

Study Registration Dates

• First Submitted: October 27, 2019
• First Submitted That Met QC Criteria: October 27, 2019
• First Posted (ACTUAL): October 30, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 24, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Nasopharyngeal Neoplasms; Carcinoma; Nasopharyngeal Carcinoma
• Other Study ID Numbers: SPHIC-TR-HNCNS-2019-34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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.
• IPD Sharing Time Frame: Within 3 years after publication of the study.
• IPD Sharing Access Criteria: 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No