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Nasopharyngeal NeoplasmsPhase 3CONTINUUMNCT03700476

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

A Phase 3 study testing Sintilimab, Gemcitabine and Cisplatin in people with Nasopharyngeal Neoplasms, run by Sun Yat-sen University at 9 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Nasopharyngeal Neoplasms
What is being tested?
Sintilimab, Gemcitabine and Cisplatin
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
425 participants
Where
9 sitesChina
Study dates
21 Dec 2018to Jan 2025
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

China9 sites

  • Xiangya Hospital Central South University

    Changsha, Hunan

  • West China Hospital, Sichuan University

    Chengdu, Sichuan

  • First People's Hospital of Foshan

    Foshan, Guangdong

  • Panyu central hospital

    Guangzhou, Guangdong, 510060

  • SUN YAT-SEN UNIVERSITY cANCER CENTER

    Guangzhou, Guangdong, 510060

  • Cancer Hospital of Guizhou Medical University

    Guiyang, Guizhou

  • Cancer Hospital of Guangxi Medical University

    Nanning, Guangxi

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

    Wuhan, Hubei

  • Xijing Hospital, Fourth Military Medical University

    Xi’an, Shanxi

Other trials in China

About this study

Official title: Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma: a Randomized, Multicenter, Phase 3 Trial

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.

Being tested
Sintilimab, Gemcitabine, Cisplatin, intensity-modulated radiotherapy
Medical subject headings
Nasopharyngeal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SintilimabDrug

    Also called IBI308, PD-1 antibody

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

  • GemcitabineDrug

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

  • CisplatinDrug

    Also called DDP

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

  • intensity-modulated radiotherapyRadiation

    Also called IMRT

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

Study groups in NCT03700476
Study groupRoleWhat they receive
Sintilimab armExperimentalPatients 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.
Receives: Drug: Sintilimab; Drug: Gemcitabine; Drug: Cisplatin; Radiation: intensity-modulated radiotherapy
Chemoradiation armActive comparatorPatients 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.
Receives: Drug: Gemcitabine; Drug: Cisplatin; Radiation: intensity-modulated radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free survival (EFS)

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

    Measured: 3 years

Secondary outcomes (6)

  1. Overall survival (OS)

    calculated from randomization to the date of death from any cause.

    Measured: 3 years

  2. Distant metastasis-free survival (DMFS)

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

    Measured: 3 years

  3. Locoregional recurrence-free survival (LRFS)

    calculated from randomization to the date of locoregional persistence, 1st locoregional recurrence, or death from any cause, whichever occurred first.

    Measured: 3 years

  4. Adverse events (AEs) and serious adverse events (SAEs)

    Graded according to CTCAE V5.0.

    Measured: 3 years

  5. Quality of life (QoL)

    The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 34 weeks (at the end of sintilimab treatment in the sintilimab arm and the corresponding timepoint in the chemoradiation arm), 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.

    Measured: 3 years

  6. Event-free survival (EFS) within different subgroups

    analyses for EFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (<4000copies/ml vs. ≥4000copies/ml), different PD-L1 expression levels (<1% vs. ≥1%), tertiary lymphoid structure (+ vs. -), age, gender, performance status, T category, N category, and stage (III vs. IVA).

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2018
  2. Study start21 Dec 2018
  3. Primary completion28 Feb 2023
  4. Study completionJan 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
425 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03700476
Sponsor's protocol ID
2018-FXY-135-FLK
Acronym
CONTINUUM
Status last verified
Mar 2023
First submitted
3 Oct 2018
Last updated
28 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Complete de-identified patient data set

Publications

  • Huang SW, Liang YL, Tao YL, Li WF, Zhou GQ, Mao YP, Guo R, Chen L, Xu S, Liu X, Zhang N, Liu F, Shen LF, Zhou YY, Yuan YW, Zou GR, Jin F, Tang LL, Sun Y, Li YQ, Ma J, Liu N. Development of a Classifier for Metabolic Subtypes of Nasopharyngeal Carcinoma to Guide Personalized Immunotherapy Strategies: Biomarker Analysis of the Phase III CONTINUUM and DIPPER Trials. J Clin Oncol. 2026 Apr 10;44(11):1028-1039. doi: 10.1200/JCO-25-02111. Epub 2026 Mar 6.

    PubMed 41791006

  • 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.

    PubMed 40651471

  • 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.

    PubMed 39438442

  • 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.

    PubMed 38824941

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Sintilimab, Gemcitabine and Cisplatin in people with Nasopharyngeal Neoplasms, run by Sun Yat-sen University at 9 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 28 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (EFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03700476, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Mar 2023.

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