Chemoradiotherapy Plus Anti-PD1 in Recurrent NPC: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

Chemoradiotherapy Combined With Programmed Death 1 Antibody in Recurrent Nasopharyngeal Carcinoma: A Multicenter, Open-label, Randomised, Controlled, Phase III Trial

This is a multicenter, open-label, randomized, controlled, phase III trial. The purpose of this trial is to evaluate the efficacy and toxicity of anti-PD-1 antibody combined with chemoradiotherapy versus chemoradiotherapy alone in recurrent nasopharyngeal carcinoma patients.

Study Overview

• Status: Recruiting
• Conditions: Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Toripalimab; Drug: Chemotherapy; Radiation: Intensity modulated radiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 212
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jingjing Miao, PhD; Phone Number: +8613631355201; Email: miaojj@sysucc.org.cn

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking University Third Hospital
    • Contact: Suqing Tian
  • Chengdu, China
    • Not yet recruiting
    • Sichuan Cancer Hospital
    • Contact: Shun Lu
  • Fuzhou, China
    • Not yet recruiting
    • Fujian Province Cancer Hospital
    • Contact: Shaojun Lin
  • Guiyang, China
    • Not yet recruiting
    • Guizhou Cancer Hospital
    • Contact: Feng Jin
  • Hangzhou, China
    • Recruiting
    • Zhejiang Cancer Hospital
    • Contact: Xiaozhong Chen
  • Nanchang, China
    • Recruiting
    • Jiangxi Cancer Hospital
    • Contact: Jingao Li
  • Nanning, China
    • Recruiting
    • The First Affiliated Hospital of Guangxi Medical University
    • Contact: Rengshen Wang
  • Shanghai, China
    • Not yet recruiting
    • Fudan University Shanghai Cancer Center
    • Contact: Chaosu Hu
  • Wuhan, China
    • Recruiting
    • Zhongnan Hospital of Wuhan University
    • Contact: Conghua Xie
  • Xi'an, China
    • Recruiting
    • Xijing Hospital
    • Contact: Mei Shi
  • Xiamen, China
    • Not yet recruiting
    • The First Affiliated Hospital of Xiamen University
    • Contact: Qin Lin
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-Sen University Cancer Center
      • Contact: Jingjing Miao, PhD; Phone Number: 13631355201; Email: miaojj@sysucc.org.cn
      • Principal Investigator: Chong Zhao, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosed as local with or without regional recurrence after ≥1 year of radical treatment;
• Not suitable for surgery;
• Histologic diagnosis of NPC (WHO II/III);
• TNM stage rII-IVa (AJCC/UICC 8th);
• ECOG 0-1 point;
• No treatment to rNPC prior, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
• No contraindications to immunotherapy or chemoradiotherapy;
• Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
• Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
• Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
• Take effective contraceptions during and two months after treatment;
• Patients must be informed of the investigational nature of this study and give written informed consent.

Exclusion Criteria:

• Treated with anti-tumor Chinese medicine treatment;
• Have recurrence with local necrosis;
• Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
• Unexplained fever > 38.5, except for tumor fever;
• Treated with ≥ 5 days antibiotics one month before enrollment;
• Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy); Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive; Have previously treated with PD-1 antibody or other immunotherapy for PD-1/PD-L1 pathway;
• Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
• Have known allergy to large molecule protein products or any compound of study therapy;
• Pregnant or breastfeeding;
• Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
• Have received a live vaccine within 30 days of planned start of study therapy Has psychiatric drug or substance abuse disorders that would interfere with cooperation with the requirements of the trial;
• Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemoradiotherapy+anti-PD-1; Patients in this arm will receive three cycles of GP chemotherapy plus PD-1 antibody, then receive IMRT and PD-1 antibody maintenance for eight cycles.	Drug: Toripalimab; 240mg, D1, every 3 weeks per cycle, three cycles with chemotherapy and eight cycles after IMRT; Other Names: JS001; Drug: Chemotherapy; Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles; Other Names: GP; Radiation: Intensity modulated radiotherapy; total 60-66Gy, 1.8-2.0Gy/f/day; Other Names: IMRT
Active Comparator: Chemoradiotherapy; Patients in this arm will receive three cycles of GP chemotherapy, then receive IMRT.	Drug: Chemotherapy; Gemcitabine: 1.0g/m2, D1 and D8, Cisplatin 80mg/m2, D1, every 3 weeks per cycle, total three cycles; Other Names: GP; Radiation: Intensity modulated radiotherapy; total 60-66Gy, 1.8-2.0Gy/f/day; Other Names: IMRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Defined as the time from date of recruitment to death from any cause.	three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Failure-free survival	Defined as the time from date of recruitment to documented relapse or death from any cause.	three years
Objective response rate through study completion, an average of nine months	The rate of patients get CR or PR after treatment	through study completion, an average of nine months
Disease control rate through study completion, an average of nine months	The rate of patients get CR or PR or SD after treatment	through study completion, an average of nine months
Incidence of nasopharyngeal necrosis and hemorrhage up to 3 years	Incidence of nasopharyngeal necrosis and hemorrhage after receiving treatment	up to three-year follow-up
Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0)	Acute toxicities were graded using the Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0) for chemotherapy and immunotherapy-specific toxicities, and the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria for radiotherapy-specific toxicities.	through study completion, an average of nine months
Late toxicity	Late toxicities were assessed annually using the RTOG radiation morbidity scoring criteria.	three years
Quality of life through study completion, up to 3 years	Evaluated with questionnaire of EuroQoL 5 dimension, 5 level health state utility index (EQ-5D-5L).	up to three-year follow-up

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Chong Zhao, MD PhD, Sun Yat-Sen University Cancer Center

Publications and helpful links

Helpful Links

• Home Page of Sun Yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 9, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: efficacy; chemoradiotherapy; toxicity; nasopharyngeal carcinoma; locoregional relapse; PD-1 antibody
• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Therapeutics; Radiotherapy; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; toripalimab; Drug Therapy; Radiotherapy, Intensity-Modulated
• Other Study ID Numbers: B2022-111-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No