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

NCT ID: NCT03700476

Last Updated: 2023-03-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

425 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-21

Study Completion Date

2025-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Nasopharyngeal Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sintilimab arm

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.

Group Type EXPERIMENTAL

Sintilimab

Intervention Type DRUG

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

Gemcitabine

Intervention Type DRUG

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

Cisplatin

Intervention Type 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

intensity-modulated radiotherapy

Intervention Type RADIATION

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

Chemoradiation arm

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.

Group Type ACTIVE_COMPARATOR

Gemcitabine

Intervention Type DRUG

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

Cisplatin

Intervention Type 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

intensity-modulated radiotherapy

Intervention Type RADIATION

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

Interventions

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Sintilimab

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

Intervention Type DRUG

Gemcitabine

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

Intervention Type DRUG

Cisplatin

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

Intervention Type DRUG

intensity-modulated radiotherapy

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

Intervention Type RADIATION

Other Intervention Names

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IBI308 PD-1 antibody DDP IMRT

Eligibility Criteria

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Inclusion Criteria

1. Patients with histologically confirmed nasopharyngeal carcinoma.
2. Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
3. Eastern Cooperative Oncology Group performance status ≤1.
4. Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
5. Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
6. Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
7. Patients must be informed of the investigational nature of this study and give written informed consent.
8. 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.

Exclusion Criteria

1. Age \> 65 or \< 18.
2. Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA \>1×10e3 copies/ml or 200IU/ml
3. Hepatitis C virus (HCV) antibody positive
4. 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).
5. 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.
6. 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.
7. Has a known history of interstitial lung disease.
8. Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
9. Is pregnant or breastfeeding.
10. Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer, and papillary thyroid carcinoma.
11. Has known allergy to large molecule protein products or any compound of sintilimab.
12. Has a known history of human immunodeficiency virus (HIV) infection.
13. 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Innovent Biologics (Suzhou) Co. Ltd.

INDUSTRY

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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Jun Ma, MD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jun Ma, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

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First People's Hospital of Foshan

Foshan, Guangdong, China

Site Status

Panyu central hospital

Guangzhou, Guangdong, China

Site Status

SUN YAT-SEN UNIVERSITY cANCER CENTER

Guangzhou, Guangdong, China

Site Status

Cancer Hospital of Guangxi Medical University

Nanning, Guangxi, China

Site Status

Cancer Hospital of Guizhou Medical University

Guiyang, Guizhou, China

Site Status

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

Wuhan, Hubei, China

Site Status

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status

Xijing Hospital, Fourth Military Medical University

Xi’an, Shanxi, China

Site Status

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status

Countries

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China

References

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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 Jul 11:100770. doi: 10.1016/j.medj.2025.100770. Online ahead of print.

Reference Type DERIVED
PMID: 40651471 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39438442 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38824941 (View on PubMed)

Other Identifiers

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2018-FXY-135-FLK

Identifier Type: -

Identifier Source: org_study_id

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