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

Nasopharyngeal Neoplasms Clinical Trial

— CONTINUUM  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03700476
• Other study ID #: 2018-FXY-135-FLK
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 21, 2018
• Est. completion date: January 2025

Study information

• Verified date: March 2023
• Source: Sun Yat-sen University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 425
• Est. completion date: January 2025
• Est. primary completion date: February 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms

Intervention

Drug:
• Sintilimab
Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.
• Gemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
• 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

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

Locations

Country	Name	City	State
China	Xiangya Hospital Central South University	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	First People's Hospital of Foshan	Foshan	Guangdong
China	Panyu central hospital	Guangzhou	Guangdong
China	SUN YAT-SEN UNIVERSITY cANCER CENTER	Guangzhou	Guangdong
China	Cancer Hospital of Guizhou Medical University	Guiyang	Guizhou
China	Cancer Hospital of Guangxi Medical University	Nanning	Guangxi
China	Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei
China	Xijing Hospital, Fourth Military Medical University	Xi'an	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Sun Yat-sen University	Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The association of circulation autoimmune antibodies with immune-related adverse events		1 year
Other	The association of circulation cytokines, chemokines, and growth factors/regulators with immune-related adverse events		1 year
Other	The association of gene expression with the efficacy of sintilimab	RNA sequencing will be conducted using baseline tumor samples.	3 years
Other	The association of cell populations with the efficacy of sintilimab	Multiplex Immunofluorescence will be conducted to assess tumor and immune-related markers in baseline tumor samples.	3 years
Primary	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	Overall survival (OS)	calculated from randomization to the date of death from any cause.	3 years
Secondary	Distant metastasis-free survival (DMFS)	calculated from randomization to the date of first distant metastasis, or death from any cause, whichever occurred first.	3 years
Secondary	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.	3 years
Secondary	Adverse events (AEs) and serious adverse events (SAEs)	Graded according to CTCAE V5.0.	3 years
Secondary	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.	3 years
Secondary	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).	3 years