Carbon-Ion Radiotherapy Plus Camrelizumab With or Without Apatinib for Locally Recurrent Nasopharyngeal Carcinoma

Brief Title

Carbon-Ion Radiotherapy Plus Camrelizumab for Locally Recurrent Nasopharyngeal Carcinoma

Official Title

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

Brief 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).
    

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 Phase

Phase 2

Study Type

Interventional

Primary Outcome

Progression-free survival

Secondary Outcome

 Overall survival

Condition

Nasopharyngeal Carcinoma

Intervention

Induction chemotherapy

Study Arms / Comparison Groups

 Arm-C

Description:  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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

146

Start Date

January 20, 2021

Completion Date

December 20, 2025

Primary Completion Date

December 20, 2025

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
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

Jiade J Lu, MD, +8602138296666, [email protected]

Location Countries

China

Location Countries

China

NCT ID

NCT04143984

Organization ID

SPHIC-TR-HNCNS-2019-34

Responsible Party

Principal Investigator

Study Sponsor

Shanghai Proton and Heavy Ion Center

Study Sponsor

Jiade J Lu, MD, Principal Investigator, Shanghai Proton and Heavy Ion Center

Verification Date

January 2021