Clinical trial NCT03700476: Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma
Official title: Sintilimab (PD-1 Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma: a Randomized, Multicenter, Phase 3 Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Nasopharyngeal Neoplasms
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Innovent Biologics (Suzhou) Co. Ltd.
First posted: 2018-10-09
Enrollment: 425
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Event-free survival (EFS)
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 3 years
measure: Distant metastasis-free survival (DMFS)
timeFrame: 3 years
measure: Locoregional recurrence-free survival (LRFS)
timeFrame: 3 years
measure: Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 3 years
measure: Quality of life (QoL)
timeFrame: 3 years
measure: Event-free survival (EFS) within different subgroups
timeFrame: 3 years
Other outcomes:
measure: The association of circulation autoimmune antibodies with immune-related adverse events
timeFrame: 1 year
measure: The association of circulation cytokines, chemokines, and growth factors/regulators with immune-related adverse events
timeFrame: 1 year
measure: The association of gene expression with the efficacy of sintilimab
timeFrame: 3 years
measure: The association of cell populations with the efficacy of sintilimab
timeFrame: 3 years
Locations:
city: Foshan
country: China
facility: First People's Hospital of Foshan
state: Guangdong
city: Guangzhou
country: China
facility: Panyu central hospital
state: Guangdong
city: Guangzhou
country: China
facility: SUN YAT-SEN UNIVERSITY cANCER CENTER
state: Guangdong
city: Nanning
country: China
facility: Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Guiyang
country: China
facility: Cancer Hospital of Guizhou Medical University
state: Guizhou
city: Wuhan
country: China
facility: Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Xi'an
country: China
facility: Xijing Hospital, Fourth Military Medical University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: Sun Yat-sen University
name: Jun Ma, MD
role: PRINCIPAL_INVESTIGATOR
References: