Nasopharyngeal Cancinoma (NPC), Nasopharangeal Cancer
Conditions
Keywords
adebrelimab, PD-L1 antibody, chemoradiotherapy, capecitabine
Brief summary
This trial evaluated the efficacy of two adjuvant regimens following identical induction and concurrent chemoradiotherapy (IC+CCRT) in locoregionally advanced nasopharyngeal carcinoma (LANPC) patients with persistent EBV DNA positivity or stable disease after three IC cycles. The control arm received adjuvant adebrelimab, while the experimental arm received adebrelimab plus capecitabine.
Detailed description
This study will enroll patients with stage II-III LANPC (AJCC 9th edition, excluding T3N0-1). After three cycles of induction chemotherapy (gemcitabine, cisplatin, and adebrelimab), eligible patients with persistent EBV DNA or stable disease will be randomized 1:1. All patients will undergo CCRT followed by adjuvant therapy. The control arm will receive five cycles of adebrelimab. The experimental arm will receive five cycles of adebrelimab in combination with capecitabine, which will be administered for one year.
Interventions
Adebrelimab 1200mg will be given every 3 weeks for 5 cycles in adjuvant chemotherapy
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.
DRUGCapecitabine
Capecitabine was administered at 650 mg/m² orally twice daily for one year.
Sponsors
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. Age ≥18 and ≤65 years 2. Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria. 3. Eastern Cooperative Oncology Group performance score of 0-1. 4. Tumor staged as II-III disease (AJCC 9th edition), excluding T3N0-1. 5. Adequate marrow function: white blood cell count \> 4 × 10⁹/L hemoglobin \>90g/L and platelet count \>100×10⁹/L 6. Adequate hepatic and renal function： * Total bilirubin ≤ 1.5 × upper limit of normal (ULN) * Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) ≤2.5×ULN * Alkaline phosphatase ≤ 2.5 × ULN * clearance rate ≥ 60 ml/min 7. Other laboratory and clinical criteria * Normal thyroid function, serum amylase and lipase, pituitary hormone levels, inflammatory markers, cardiac enzyme tests and electrocardiogram (ECG) * For patients aged \>50 years with a history of smoking, normal pulmonary function test (PFT) results are required * For patients with abnormal ECG findings or a prior history of cardiovascular disease (not meeting any
Exclusion criteria
listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits 8. Patients with persistent EBV DNA positivity or stable disease following 3 cycles of induction chemotherapy (gemcitabine, cisplatin, and adebrelimab). 9. Patients must be informed of the investigational nature of this study and give written informed consent, and be willing and able to comply with the study schedule, including follow-up visits, treatment procedures, laboratory testing, and other protocol-related requirements. 10. Women of childbearing potential (WOCBP) must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of study drug (e.g., condoms, physician-guided regular use of oral contraceptives).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free survival (FFS) | 3 year | From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first, assessed up to 74 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free survival (FFS) within different subgroups | 3 years | analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (≤4000copies/ml vs. \>4000copies/ml), different PD-L1 expression levels, age, gender, performance status, T category, N category, and stage. |
| Adverse events (AEs) and serious adverse events (SAEs) | 3 years | Graded according to CTCAE V5.0. |
| Quality of life (QoL) | week 1, 6, 24, 60, 72 | The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 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. For the functional scales and the global health status scale, a higher score represents a better level of functioning or quality of life. For the symptom scales, a higher score indicates a greater severity of symptoms. |
| Overall survival (OS) | 3 years | From date of randomization until the date of death from any cause, whichever came first, assessed up to 74 months |
| Distant metastasis-free survival (DMFS) | 3 years | From date of randomization until the date of first documented distant metastasis, whichever occurred first, assessed up to 74 months. |
| Locoregional recurrence-free survival (LRRFS) | 3 years | From date of randomization until the date of first documented locoregional recurrence, whichever occurred first, assessed up to 74 months. |
| Tumor response | the time of completion of induction chemotherapy, radiotherapy, and adjuvant immunotherapy; from the date of enrollment until the date of the last time that tumorimaging and assessment of disease has been done, assessed up to 74 weeks | Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians |
Other
| Measure | Time frame | Description |
|---|---|---|
| Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level | 3 years | Subgroup analysis |
| Correlation between pre-treatment PD-L1 expression level and FFS | 3 years | Pre-treatment PD-L1 expression level of tumor cell is evaluated centrally by means of immunohistochemical testing. |
Contacts
Primary ContactJun Ma, M.D
Backup ContactLei Chen, M.D.
Outcome results
None listed