Reduced-dose Radiotherapy for Stage III Nasopharyngeal Carcinoma Based on the Treatment Response

NCT06239727 | Recruiting Phase 3 DMC

• 1 other identifier: 2023-FXY-204-FLK
• Study Type: interventional
• Target: 593
• Locations: 1 country
• Sites: 26

Brief Summary

This is an Open Label, Non-Inferiority, Multicenter, Randomized Phase 3 Trial aimed to investigate the impact of reduced-dose radiotherapy in combination with chemotherapy and immunotherapy on patients' prognosis and complication compared with conventional-dose radiotherapy in combination with chemotherapy and immunotherapy for treatment-sensitive stage III NPC patients screened out according to the treatment response.

Conditions

Nasopharyngeal Carcinoma

Keywords

Radiotherapy; Dose; PD-1; Immune Checkpoint Inhibitor; Capecitabine; Quality of Life; Personalised Therapy; Complication; Deintensification

Outcome Measures

Primary Outcomes (1)

• Locoregional failure-free survival (LRFFS)

  Locoregional failure-free survival is measured from day of diagnosis until local or regional recurrence.

  3-year

Secondary Outcomes (8)

• Overall survival (OS)

  3 year

• Failure-free survival (FFS)

  3 year

• Distant failure-free survival (DFFS)

  3 year

• Local failure-free survival (LFFS)

  3 year

• Regional failure-free survival (RFFS)

  3 year

Study Arms (3)

Reduced-dose radiotherapy group

EXPERIMENTAL

All participants will receive induction chemotherapy and immunotherapy (every 3 weeks × 3 cycles of gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1 + camrelizumab 200 mg day 1) followed by reduced-dose intensity-modulated radiation therapy (IMRT; 6360cGy, 30 fractions, 5 fractions/week, 1 fraction/day). During the radiotherapy, all the participants will receive concurrent chemotherapy (every 3 weeks × 2 cycles of cisplatin 100 mg/m2 day 1). After 3 weeks of the completion of concurrent chemoradiotherapy, adjuvant camrelizumab (200 mg per cycle) will be administrated every 3 weeks for 9 cycles.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin (80 mg/m2); Radiation: Reduced-dose Intensity-modulated radiotherapy; Drug: Cisplatin (100 mg/m2)

Conventional-dose radiotherapy group

ACTIVE COMPARATOR

All participants will receive induction chemotherapy and immunotherapy (every 3 weeks × 3 cycles of gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1 + camrelizumab 200 mg day 1) followed by conventional-dose intensity-modulated radiation therapy (IMRT; 6996cGy, 33 fractions, 5 fractions/week, 1 fraction/day). During the radiotherapy, all the participants will receive concurrent chemotherapy (every 3 weeks × 2 cycles of cisplatin 100 mg/m2 day 1). After 3 weeks of the completion of concurrent chemoradiotherapy, adjuvant camrelizumab (200 mg per cycle) will be administrated every 3 weeks for 9 cycles.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin (80 mg/m2); Radiation: Conventional-dose Intensity-modulated radiotherapy; Drug: Cisplatin (100 mg/m2)

Not-Randomized population

OTHER

All participants will receive induction chemotherapy and immunotherapy (every 3 weeks × 3 cycles of gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1 + camrelizumab 200 mg day 1) followed by conventional-dose intensity-modulated radiation therapy (IMRT; 6996cGy, 33 fractions, 5 fractions/week, 1 fraction/day). During the radiotherapy, all the participants will receive concurrent chemotherapy (every 3 weeks × 2 cycles of cisplatin 100 mg/m2 day 1). After 3 weeks of the completion of concurrent chemoradiotherapy, adjuvant camrelizumab (200 mg per cycle) will be administrated every 3 weeks for 9 cycles. Besides, all the participants should also receive metronomic adjuvant capecitabine chemotherapy (capecitabine 650 mg/m2 p.o. BID 1 year) immediately after the completion of concurrent chemoradiotherapy.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin (80 mg/m2); Radiation: Conventional-dose Intensity-modulated radiotherapy; Drug: Cisplatin (100 mg/m2); Drug: Capecitabine

Interventions

PD-1 blocking antibody DRUG

1. IC phase of PD-1 blocking antibody: every 3 weeks × 3 cycles; 200 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 3 cycles till the end of IC. 2. Adjuvant PD-1 blocking antibody: every 3 weeks × 9 cycles; 200 mg, day 1.

Also known as: Camrelizumab

Conventional-dose radiotherapy group; Not-Randomized population; Reduced-dose radiotherapy group

Gemcitabine DRUG

Gemcitabine as induction chemotherapy, 1000 mg/m2 day 1, 8 per cycle, every 3 weeks for 3 cycles.

Also known as: GEM

Conventional-dose radiotherapy group; Not-Randomized population; Reduced-dose radiotherapy group

Cisplatin (80 mg/m2) DRUG

Cisplatin as induction chemotherapy, 80 mg/m2 day 1 per cycle, every 3 weeks for 3 cycles.

Also known as: DDP

Conventional-dose radiotherapy group; Not-Randomized population; Reduced-dose radiotherapy group

Reduced-dose Intensity-modulated radiotherapy RADIATION

1. Definitive IMRT, 30 fractions, 5 fractions/week, 1 fraction/day 2. Radiotherapy dose: pGTV: 6360cGy/30F; pCTV1: 5460cGy/30F; pCTV2: 4920cGy/30F.

Also known as: Reduced-dose IMRT

Reduced-dose radiotherapy group

Cisplatin (100 mg/m2) DRUG

Cisplatin as concurrent chemotherapy, 100 mg/m2 day 1 per cycle, every 3 weeks for 2 cycles

Also known as: DDP

Conventional-dose radiotherapy group; Not-Randomized population; Reduced-dose radiotherapy group

Conventional-dose Intensity-modulated radiotherapy RADIATION

1. Definitive IMRT, 33 fractions, 5 fractions/week, 1 fraction/day 2. Radiotherapy dose: pGTV: 6996cGy/33F; pCTV1: 6006cGy/33F; pCTV2: 5412cGy/33F.

Also known as: Conventional-dose IMRT

Conventional-dose radiotherapy group; Not-Randomized population

Capecitabine DRUG

Metronomic adjuvant capecitabine chemotherapy: 650 mg/m2 p.o. bid, 1 year, adminstration starts immediately after concurrent chemoradiotherapy.

Not-Randomized population

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18 Years to 65 Years;
• Eastern Cooperative Oncology Group performance status ≤1;
• Patients with newly diagnosed, histologically confirmed nasopharyngeal carcinoma, the pathological type is non-keratinising carcinoma;
• Tumor staged as Stage III (T3N0 Excepted; AJCC 8th);
• Patients' lymph node without adverse features (no central necrosis, no muscle/skin invasion, no lymph node fusion);
• Normal bone marrow function: white blood cell count \> 4×10\^9/L, hemoglobin \> 90g/L, platelet count \> 100×10\^9/L;
• Normal liver and kidney function: total bilirubin ≤ 1.5 × upper limit of normal (ULN), alanine transaminase and aspartate transaminase ≤ 2.5 × ULN, alkaline phosphatase ≤ 2.5 × ULN, creatinine clearance rate ≥ 60 ml/min;
• Receive 3 cycles of indction chemotherapy (GP regimen + Camrelizumab);
• Plasma EBV DNA after the second cycle of concurrent chemotherapy: negative;
• Complete remission after 27 fractions of radiotherapy based on the MRI examination of the nasopharynx and neck (According to Response Evaluation Criteria in Solid Tumors 1.1);
• Patients must sign informed consent and be willing and able to comply with the requirements of visits, treatment, laboratory tests and other research requirements stipulated in the research schedule;
• Subjects with pregnancy ability must agree to use reliable contraceptive measures from screening to 1 year after treatment.

You may not qualify if:

• Hepatitis B virus surface antigen (HBsAg) positive and Hepatitis B virus DNA \> 1000 copies/ml;
• Anti-hepatitis C virus positive;
• Anti-human immunodeficiency virus (HIV) positive or diagnosed with acquired immune deficiency syndrome (AIDS);
• Active tuberculosis: active tuberculosis in the past 1 year should be excluded regardless with treatment, history of active tuberculosis over 1 year should be excluded except that previous regulatory anti-tuberculosis treatment is proved;
• Active, known or suspected autoimmune disease (including but not limited to uveitis, enteritis, hepatitis, pituitary, nephritis, vasculitis, hyperthyroidism, hypothyroidism and asthma requiring bronchiectasis). Exceptions are type I diabetes mellitus, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment (such as vitiligo, psoriasis or alopecia);
• Previous interstitial lung disease or pneumonia requiring oral or intravenous steroid therapy;
• Chronic treatment with systemic glucocorticoid (dose equivalent to or over 10 mg prednisone per day) or any other form of immunosuppressive therapy. Subjects who used inhaled or topical corticosteroids were eligible;
• Uncontrolled heart disease, for example: 1) heart failure (NYHA level ≥ 2), 2) unstable angina, 3) myocardial infarction in past 1 year, 4) supraventricular or ventricular arrhythmia requiring treatment or intervention;
• Active infection requiring systemic treatment;
• Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
• History of radiotherapy, except for non-melanoma skin cancer located outside the target volume of radiotherapy for nasophayngeal carcinoma;
• Receive treatment for the local or regional disease other than that specified in the research plan;
• Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
• Allergy to macromolecular protein preparations, or any component of Camrelizumab;
• Receiving live vaccine within 30 days of the initial Camrelizumab;

Sponsors & Collaborators

• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator
• Sun Yat-sen University: lead

Study Sites (26)

Fujian Cancer Hospital

Fuzhou, Fujian, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

RECRUITING

Dongguan People's Hospital

Dongguan, Guangdong, China

RECRUITING

The First People's Hospital of Foshan

Foshan, Guangdong, 528000, China

RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

The Affiliated Panyu Central Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 511400, China

RECRUITING

Cancer Hospital of Shantou University Medical College

Shantou, Guangdong, China

RECRUITING

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, China

RECRUITING

Guangdong Nongken Central Hospital

Zhanjiang, Guangdong, China

RECRUITING

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

RECRUITING

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

RECRUITING

The Second Affiliated Hospital of Hainan Medical University

Haikou, Hainan, China

RECRUITING

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

RECRUITING

Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, China

RECRUITING

Jiangsu Provinee Hospital of Chinese Medicine

Nanjing, Jiangsu, China

RECRUITING

Jiangxi Cancer Center

Nanchang, Jiangxi, China

RECRUITING

The First Affiliated Hospital of Xian Jiaotong University

Xian, Shanxi, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, Sichuan, China

RECRUITING

West China Hospital，Sichuan University

Chengdu, Sichuan, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Chongqing Cancer Hospital

Chongqing, China

RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

RECRUITING

Related Publications (9)

• Ma BBY, Lim WT, Goh BC, Hui EP, Lo KW, Pettinger A, Foster NR, Riess JW, Agulnik M, Chang AYC, Chopra A, Kish JA, Chung CH, Adkins DR, Cullen KJ, Gitlitz BJ, Lim DW, To KF, Chan KCA, Lo YMD, King AD, Erlichman C, Yin J, Costello BA, Chan ATC. Antitumor Activity of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma: An International, Multicenter Study of the Mayo Clinic Phase 2 Consortium (NCI-9742). J Clin Oncol. 2018 May 10;36(14):1412-1418. doi: 10.1200/JCO.2017.77.0388. Epub 2018 Mar 27.

  PMID: 29584545 RESULT

• Hsu C, Lee SH, Ejadi S, Even C, Cohen RB, Le Tourneau C, Mehnert JM, Algazi A, van Brummelen EMJ, Saraf S, Thanigaimani P, Cheng JD, Hansen AR. Safety and Antitumor Activity of Pembrolizumab in Patients With Programmed Death-Ligand 1-Positive Nasopharyngeal Carcinoma: Results of the KEYNOTE-028 Study. J Clin Oncol. 2017 Dec 20;35(36):4050-4056. doi: 10.1200/JCO.2017.73.3675. Epub 2017 Aug 24.

  PMID: 28837405 RESULT

• Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, Xiong J, Li P, Zhao H, Huang Y, Zhang Y, Chen L, Zhou N, Zhao Y, Hou X, Yang Q, Zhang L. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018 Oct;19(10):1338-1350. doi: 10.1016/S1470-2045(18)30495-9. Epub 2018 Sep 10.

  PMID: 30213452 RESULT

• Wang FH, Wei XL, Feng J, Li Q, Xu N, Hu XC, Liao W, Jiang Y, Lin XY, Zhang QY, Yuan XL, Huang HX, Chen Y, Dai GH, Shi JH, Shen L, Yang SJ, Shu YQ, Liu YP, Wang W, Wu H, Feng H, Yao S, Xu RH. Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02). J Clin Oncol. 2021 Mar 1;39(7):704-712. doi: 10.1200/JCO.20.02712. Epub 2021 Jan 25.

  PMID: 33492986 RESULT

• Li XY, Luo DH, Guo L, Mo HY, Sun R, Guo SS, Liu LT, Yang ZC, Yang JH, Qiu F, Sun XS, Wang P, Liu Q, Li JB, Tang QN, Lin C, Yang Q, Liu SL, Liang YJ, Jia GD, Wen DX, Guo CY, Yan JJ, Zhao C, Chen QY, Tang LQ, Mai HQ. Deintensified Chemoradiotherapy for Pretreatment Epstein-Barr Virus DNA-Selected Low-Risk Locoregionally Advanced Nasopharyngeal Carcinoma: A Phase II Randomized Noninferiority Trial. J Clin Oncol. 2022 Apr 10;40(11):1163-1173. doi: 10.1200/JCO.21.01467. Epub 2022 Jan 6.

  PMID: 34990291 RESULT

• Tang LL, Guo R, Zhang N, Deng B, Chen L, Cheng ZB, Huang J, Hu WH, Huang SH, Luo WJ, Liang JH, Zheng YM, Zhang F, Mao YP, Li WF, Zhou GQ, Liu X, Chen YP, Xu C, Lin L, Liu Q, Du XJ, Zhang Y, Sun Y, Ma J. Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA. 2022 Aug 23;328(8):728-736. doi: 10.1001/jama.2022.13997.

  PMID: 35997729 RESULT

• Tang LL, Huang CL, Zhang N, Jiang W, Wu YS, Huang SH, Mao YP, Liu Q, Li JB, Liang SQ, Qin GJ, Hu WH, Sun Y, Xie FY, Chen L, Zhou GQ, Ma J. Elective upper-neck versus whole-neck irradiation of the uninvolved neck in patients with nasopharyngeal carcinoma: an open-label, non-inferiority, multicentre, randomised phase 3 trial. Lancet Oncol. 2022 Apr;23(4):479-490. doi: 10.1016/S1470-2045(22)00058-4. Epub 2022 Feb 28.

  PMID: 35240053 RESULT

• Mao YP, Wang SX, Gao TS, Zhang N, Liang XY, Xie FY, Zhang Y, Zhou GQ, Guo R, Luo WJ, Li YJ, Liang SQ, Lin L, Li WF, Liu X, Xu C, Chen YP, Lv JW, Huang SH, Liu LZ, Li JB, Tang LL, Chen L, Sun Y, Ma J. Medial retropharyngeal nodal region sparing radiotherapy versus standard radiotherapy in patients with nasopharyngeal carcinoma: open label, non-inferiority, multicentre, randomised, phase 3 trial. BMJ. 2023 Feb 6;380:e072133. doi: 10.1136/bmj-2022-072133.

  PMID: 36746459 RESULT

• Guo SS, Yang JH, Sun XS, Liu LZ, Yang ZC, Liu LT, Liu SL, Li XY, Lv XF, Luo DH, Li JB, Liu Q, Wang P, Guo L, Mo HY, Sun R, Yang Q, Liang YJ, Jia GD, Zhao C, Chen QY, Tang LQ, Mai HQ. Reduced-dose radiotherapy for Epstein-Barr virus DNA selected staged III nasopharyngeal carcinoma: A single-arm, phase 2 trial. Eur J Cancer. 2023 Nov;194:113336. doi: 10.1016/j.ejca.2023.113336. Epub 2023 Sep 9.

  PMID: 37801967 RESULT

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

camrelizumab; Gemcitabine; Cisplatin; Capecitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Jun Ma

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jun Ma

CONTACT

+862087343469; majun2@mail.sysu.edu.cn

Kai-Bin Yang

CONTACT

+8613725368062; yangkb@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 26, 2024
• First Posted: February 2, 2024
• Study Start: March 1, 2024
• Primary Completion (Estimated): February 20, 2027
• Study Completion (Estimated): February 20, 2030
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (26)