Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma

NCT03700476 | Unknown Phase 3 DMC

• 1 other identifier: 2018-FXY-135-FLK
• Study Type: interventional
• Target: 425
• Locations: 1 country
• Sites: 9

Brief Summary

The CONTINUUM trial plans to enroll patients with stage III-IVA (AJCC 8th, except T3N0-1 or T4N0) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus Sintilimab. All patients will receive intensity-modulated radiotherapy (IMRT). Sintilimab will begin on day 1 of induction chemotherapy and continue every 3 weeks for 12 cycles.

Conditions

Nasopharyngeal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Event-free survival (EFS)

  calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.

  3 years

Secondary Outcomes (6)

• Overall survival (OS)

  3 years

• Distant metastasis-free survival (DMFS)

  3 years

• Locoregional recurrence-free survival (LRFS)

  3 years

• Adverse events (AEs) and serious adverse events (SAEs)

  3 years

• Quality of life (QoL)

  3 years

Other Outcomes (4)

• The association of circulation autoimmune antibodies with immune-related adverse events

  1 year

• The association of circulation cytokines, chemokines, and growth factors/regulators with immune-related adverse events

  1 year

• The association of gene expression with the efficacy of sintilimab

  3 years

Study Arms (2)

Sintilimab arm

EXPERIMENTAL

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.

Drug: Sintilimab; Drug: Gemcitabine; Drug: Cisplatin; Radiation: intensity-modulated radiotherapy

Chemoradiation arm

ACTIVE COMPARATOR

Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.

Drug: Gemcitabine; Drug: Cisplatin; Radiation: intensity-modulated radiotherapy

Interventions

Sintilimab DRUG

Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.

Also known as: IBI308, PD-1 antibody

Sintilimab arm

Gemcitabine DRUG

Gemcitabine 1g/m2, d1 \& 8 of every cycle, every 3 weeks for 3 cycles before radiation.

Chemoradiation arm; Sintilimab arm

Cisplatin DRUG

Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation

Also known as: DDP

Chemoradiation arm; Sintilimab arm

intensity-modulated radiotherapy RADIATION

Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.

Also known as: IMRT

Chemoradiation arm; Sintilimab arm

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed nasopharyngeal carcinoma.
• Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
• Eastern Cooperative Oncology Group performance status ≤1.
• Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
• Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
• Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
• Patients must be informed of the investigational nature of this study and give written informed consent.
• Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.

You may not qualify if:

• Age \> 65 or \< 18.
• Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA \>1×10e3 copies/ml or 200IU/ml
• Hepatitis C virus (HCV) antibody positive
• Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
• Has any condition that required systemic corticosteroid (equivalent to prednisone \>10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
• Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB over 1 year ago will be allowed.
• Has a known history of interstitial lung disease.
• Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
• Is pregnant or breastfeeding.
• Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
• Has known allergy to large molecule protein products or any compound of sintilimab.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (9)

First People's Hospital of Foshan

Foshan, Guangdong, China

Location

Panyu central hospital

Guangzhou, Guangdong, 510060, China

Location

SUN YAT-SEN UNIVERSITY cANCER CENTER

Guangzhou, Guangdong, 510060, China

Location

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Location

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, 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

Xijing Hospital, Fourth Military Medical University

Xi’an, Shanxi, China

Location

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Location

Related Publications (3)

• Zou SQ, Huang CL, Zhang JJ, Li Z, Xiao XT, Cheng YZ, Shen JY, Wu DH, Lv JW, Tang LL, Sun Y, Li JB, Liu X, Ma J, Li WF, Chen YP. Association of anti-PD-1 therapy with severe radiation-induced oral mucositis: A retrospective cohort study and validation in the CONTINUUM trial. Med. 2025 Oct 10;6(10):100770. doi: 10.1016/j.medj.2025.100770. Epub 2025 Jul 11.

  PMID: 40651471 DERIVED

• Huang SW, Jiang W, Xu S, Zhang Y, Du J, Wang YQ, Yang KY, Zhang N, Liu F, Zou GR, Jin F, Wu HJ, Zhou YY, Zhu XD, Chen NY, Xu C, Qiao H, Liu N, Sun Y, Ma J, Liang YL, Liu X. Systemic longitudinal immune profiling identifies proliferating Treg cells as predictors of immunotherapy benefit: biomarker analysis from the phase 3 CONTINUUM and DIPPER trials. Signal Transduct Target Ther. 2024 Oct 23;9(1):285. doi: 10.1038/s41392-024-01988-w.

  PMID: 39438442 DERIVED

• Liu X, Zhang Y, Yang KY, Zhang N, Jin F, Zou GR, Zhu XD, Xie FY, Liang XY, Li WF, He ZY, Chen NY, Hu WH, Wu HJ, Shi M, Zhou GQ, Mao YP, Guo R, Sun R, Huang J, Liang SQ, Wu WL, Su Z, Li L, Ai P, He YX, Zang J, Chen L, Lin L, Huang SH, Xu C, Lv JW, Li YQ, Hong SB, Jie YS, Li H, Huang SW, Liang YL, Wang YQ, Peng YL, Zhu JH, Zang SB, Liu SR, Lin QG, Li HJ, Tian L, Liu LZ, Zhao HY, Lin AH, Li JB, Liu N, Tang LL, Chen YP, Sun Y, Ma J. Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial. Lancet. 2024 Jun 22;403(10445):2720-2731. doi: 10.1016/S0140-6736(24)00594-4. Epub 2024 May 30.

  PMID: 38824941 DERIVED

MeSH Terms

Conditions

Nasopharyngeal Neoplasms

Interventions

sintilimab; spartalizumab; Gemcitabine; Cisplatin; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; 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; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Jun Ma, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

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: October 3, 2018
• First Posted: October 9, 2018
• Study Start: December 21, 2018
• Primary Completion: February 28, 2023
• Study Completion: January 1, 2025
• Last Updated: March 28, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: For 2 years started from 12 months after publication of the primary trial report.
• Access Criteria: Authoritative researchers who provide a methodologically sound proposal for individual participant data meta-analysis.

Locations

CN (9)