Carbon-Ion Radiotherapy Plus Camrelizumab for Locally Recurrent Nasopharyngeal Carcinoma

NCT ID: NCT04143984

Last Updated: 2022-04-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-19
• Study Completion Date: 2025-12-20

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.

Conditions

Nasopharyngeal Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Induction chemotherapy

Intervention Type: DRUG

Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.

Carbon-ion radiotherapy

Intervention Type: RADIATION

Accelerated carbon-ion beam with pencil beam scanning technique.

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.

Group Type: EXPERIMENTAL

Induction chemotherapy

Intervention Type: DRUG

Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.

Carbon-ion radiotherapy

Intervention Type: RADIATION

Accelerated carbon-ion beam with pencil beam scanning technique.

Camrelizumab

Intervention Type: DRUG

An anti-PD-1 antibody.

Interventions

Induction chemotherapy

Induction chemotherapy with the regimen of gemcitabine plus nedaplatin.

Intervention Type: DRUG

Carbon-ion radiotherapy

Accelerated carbon-ion beam with pencil beam scanning technique.

Intervention Type: RADIATION

Camrelizumab

An anti-PD-1 antibody.

Intervention Type: DRUG

Other Intervention Names

SHR-1210

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Proton and Heavy Ion Center

OTHER

Sponsor Role: lead

Responsible Party

Jiade J. Lu

Prof.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jiade J Lu, MD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Proton and Heavy Ion Center

Locations

Shanghai Proton and Heavy Ion Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jiyi Hu, MD, PhD

Role: CONTACT

jiyi.hu@sphic.org.cn

+8602138296666 ext. 53513

Lin Kong, MD

Role: CONTACT

konglin@sphic.org.cn

+8602138296666 ext. 53516

Facility Contacts

Jiyi Hu, MD, PhD

Role: primary

jiyi.hu@sphic.org.cn

+8602138296666 ext. 53513

Lin Kong, MD

Role: backup

konglin@sphic.org.cn

+8602138296666 ext. 53516

References

Hu J, Huang Q, Hu W, Gao J, Yang J, Zhang H, Lu JJ, Kong L. A protocol for a randomized trial evaluating the role of carbon-ion radiation therapy plus camrelizumab for patients with locoregionally recurrent nasopharyngeal carcinoma. Cancer Med. 2024 Feb;13(3):e6742. doi: 10.1002/cam4.6742. Epub 2024 Jan 11.

Reference Type: DERIVED

PMID: 38205914 (View on PubMed)

Other Identifiers

SPHIC-TR-HNCNS-2019-34

Identifier Type: -

Identifier Source: org_study_id