Nasopharyngeal Neoplasms
Conditions
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.
Interventions
DRUGSintilimab
Sintilimab 200mg will be given every 3 weeks for 12 cycles, started on day 1 of induction chemotherapy.
DRUGGemcitabine
Gemcitabine 1g/m2, d1 & 8 of every cycle, every 3 weeks for 3 cycles before radiation.
DRUGCisplatin
Induction cisplatin 80mg/m2, every 3 weeks for 3 cycles before radiation; Concurrent cisplatin 100mg/m2, every 3 weeks for 2 cycles during radiation
RADIATIONintensity-modulated radiotherapy
Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy will be given in 33 fractions.
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (EFS) | 3 years | calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant metastasis-free survival (DMFS) | 3 years | calculated from randomization to the date of first distant metastasis, or death from any cause, whichever occurred first. |
| Locoregional recurrence-free survival (LRFS) | 3 years | calculated from randomization to the date of locoregional persistence, 1st locoregional recurrence, or death from any cause, whichever occurred first. |
| Adverse events (AEs) and serious adverse events (SAEs) | 3 years | Graded according to CTCAE V5.0. |
| Quality of life (QoL) | 3 years | 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. |
| Event-free survival (EFS) within different subgroups | 3 years | 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). |
| Overall survival (OS) | 3 years | calculated from randomization to the date of death from any cause. |
Other
| Measure | Time frame | Description |
|---|---|---|
| The association of gene expression with the efficacy of sintilimab | 3 years | RNA sequencing will be conducted using baseline tumor samples. |
| The association of cell populations with the efficacy of sintilimab | 3 years | Multiplex Immunofluorescence will be conducted to assess tumor and immune-related markers in baseline tumor samples. |
| The association of circulation cytokines, chemokines, and growth factors/regulators with immune-related adverse events | 1 year | — |
| The association of circulation autoimmune antibodies with immune-related adverse events | 1 year | — |
Countries
China
Outcome results
None listed