Nivolumab Combined With Chemoradiotherapy Sparing Concurrent Cisplatin in Nasopharyngeal Carcinoma

NCT03984357 | Completed Phase 2 DMC

• 1 other identifier: CA209-7GC
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 6

Brief Summary

This is a phase 2, single-arm, multicenter clinical trial, with the purpose to evaluate the therapeutic efficacy, safety, and tolerability of PD-1 Blockade nivolumab combined with a deintensified chemoradiotherapy by sparing concurrent cisplatin from the standard induction chemotherapy plus concurrent chemoradiotherapy in high-risk locoregionally advanced nasopharyngeal carcinoma.

Conditions

Nasopharyngeal Carcinoma

Keywords

PD-1 blockade; immune checkpoint inhibitor; induction chemotherapy; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Failure-free survival (FFS)

  Failure-free survival is measured from day of enrollment until the first indication of treatment failure (either locoregional recurrence or distant metastasis) or death from any cause, whichever occurred first

  3-year

Secondary Outcomes (6)

• Overall survival (OS)

  3-year

• Locoregional failure-free survival (LRFFS)

  3-year

• Distant failure-free survival (DFFS)

  3-year

• Incidence rate of investigator-reported adverse events (AEs)

  3-year

• Incidence rate of patient-reported adverse events (AEs)

  3-year

Other Outcomes (10)

• Correlation between pre-treatment PD-L1 expression level and FFS

  3-year

• Correlation between pre-treatment PD-L1 expression level and OS

  3-year

• Correlation between the percentage of tumor-infiltrating lymphocytes (TILs) and PFS

  3-year

Study Arms (1)

PD-1 blocking antibody combined with IC+IMRT

EXPERIMENTAL

All participants will receive induction chemotherapy (IC; every 3 weeks × 3 cycles; gemcitabine 1000 mg/m2 day 1, 8 + cisplatin 80 mg/m2 day 1) followed by intensity-modulated radiotherapy (IMRT; 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day) alone. PD-1 blocking antibody (360 mg per cycle) will start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. The first and last 3 cycles of PD-1 blocking antibody are administrated concurrently with IC and IMRT, respectively. After 4 weeks of the completion of IMRT, adjuvant PD-1 blocking antibody (480 mg per cycle) will begin every 4 weeks for 6 cycles.

Drug: PD-1 blocking antibody; Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

Interventions

PD-1 blocking antibody DRUG

1. Whole-course concurrent PD-1 blocking antibody: every 3 weeks × 6 cycles; 360 mg, day 1; start on day 1 of the first cycle IC and continue every 3 weeks for 6 cycles till the end of IMRT, involving the whole-course of IC + IMRT alone. 2. Adjuvant PD-1 blocking antibody: every 4 weeks × 6 cycles; 480 mg, day 1

Also known as: PD-1 blockade

PD-1 blocking antibody combined with IC+IMRT

Gemcitabine DRUG

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

Also known as: GEM

PD-1 blocking antibody combined with IC+IMRT

Cisplatin DRUG

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

Also known as: DDP

PD-1 blocking antibody combined with IC+IMRT

Intensity-modulated radiotherapy RADIATION

Definitive IMRT of 70 Gy, 33 fractions, 5 fractions/week, 1 fraction/day

Also known as: IMRT

PD-1 blocking antibody combined with IC+IMRT

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 to 65;
• Pathological type: non-keratinizing carcinoma (World Health Organization criteria);
• Diagnosed with LANPC (T4N1, T1-4N2-3) according to the 8th edition clinical staging system of the American Joint Committee on Cancer \[AJCC\]/Union for International Cancer Control \[UICC\];
• ECOG performance score: 0 to 1;
• Normal bone marrow function: white blood cell count \> 4×109/L, hemoglobin \> 90g/L, platelet count \> 100×109/L;

You may not qualify if:

• 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;
• 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.
• Hepatitis B virus surface antigen (HBsAg) positive and HBV DNA \> 1×10E3 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;
• Pregnant or lactating women (pregnancy test should be considered for women with sexual life and fertility);
• Previous or concurrent with other malignant tumors, except for adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary cancer;
• Allergy to macromolecular protein preparations, or any component of nivolumab;
• Active infection requiring systemic treatment;
• Receiving live vaccine within 30 days of the initial nivolumab;

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Bristol-Myers Squibb: collaborator

Study Sites (6)

Fujian Provinve Cancer Hospital

Fuzhou, Fujian Provinve, China

Location

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Location

Hubei Province Cancer Hosiptal

Wuhan, Hubei, China

Location

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

Wuhan, Hubei, China

Location

Xiangya Hospital Central South University

Changsha, Hunan, China

Location

Zhejiang Province Cancer Hospital

Hangzhou, Zhejiang, China

Location

Related Publications (8)

• Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, Peng J, Xu M, Chen D, Lu X, Wang R, Cao X, Chen X, Lin Z, Xiong J, Lin Q, Xie C, Li Z, Pan J, Li J, Wu S, Lian Y, Yang Q, Zhao C. Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: a multicentre, randomised, open-label, phase 3 trial. Lancet. 2016 Oct 15;388(10054):1883-1892. doi: 10.1016/S0140-6736(16)31388-5. Epub 2016 Aug 23.

  PMID: 27567279 BACKGROUND

• Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, Jin F, Shi M, Chen YP, Hu WH, Cheng ZB, Wang SY, Tian Y, Wang XC, Sun Y, Li JG, Li WF, Li YH, Tang LL, Mao YP, Zhou GQ, Sun R, Liu X, Guo R, Long GX, Liang SQ, Li L, Huang J, Long JH, Zang J, Liu QD, Zou L, Su QF, Zheng BM, Xiao Y, Guo Y, Han F, Mo HY, Lv JW, Du XJ, Xu C, Liu N, Li YQ, Chua MLK, Xie FY, Sun Y, Ma J. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019 Sep 19;381(12):1124-1135. doi: 10.1056/NEJMoa1905287. Epub 2019 May 31.

  PMID: 31150573 BACKGROUND

• Ma Y, Fang W, Zhang Y, Yang Y, Hong S, Zhao Y, Tendolkar A, Chen L, Xu D, Sheng J, Zhao H, Zhang L. A Phase I/II Open-Label Study of Nivolumab in Previously Treated Advanced or Recurrent Nasopharyngeal Carcinoma and Other Solid Tumors. Oncologist. 2019 Jul;24(7):891-e431. doi: 10.1634/theoncologist.2019-0284. Epub 2019 May 2.

  PMID: 31048330 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Xu C, Zhang S, Li WF, Chen L, Mao YP, Guo Y, Liu Q, Ma J, Tang LL. Selection and Validation of Induction Chemotherapy Beneficiaries Among Patients With T3N0, T3N1, T4N0 Nasopharyngeal Carcinoma Using Epstein-Barr Virus DNA: A Joint Analysis of Real-World and Clinical Trial Data. Front Oncol. 2019 Nov 29;9:1343. doi: 10.3389/fonc.2019.01343. eCollection 2019.

  PMID: 31850226 BACKGROUND

• Li XM, Zhang XM, Li JY, Jiang N, Chen L, Tang LL, Mao YP, Li WF, Zhou GQ, Li YQ, Liu N, Zhang Y, Ma J. The immune modulation effects of gemcitabine plus cisplatin induction chemotherapy in nasopharyngeal carcinoma. Cancer Med. 2022 Sep;11(18):3437-3444. doi: 10.1002/cam4.4705. Epub 2022 Mar 30.

  PMID: 35355438 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Immune Checkpoint Inhibitors; Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

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)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Jun Ma, M.D.

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 13, 2019
• Study Start: March 16, 2020
• Primary Completion: April 30, 2024
• Study Completion: March 30, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)