Nasopharyngeal Cancer, Nasopharyngeal Cancinoma (NPC)
Conditions
Keywords
Immunotherapy, PD-1/CTLA-4 Bi-specific Antibody, Chemoradiotherapy
Brief summary
The trial aimed to compare QL1706 combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in High-risk Locoregionally-Advanced Nasopharyngeal Carcinoma (LANPC).
Detailed description
The trial plans to enroll patients with stage T4N1and T1-4N2-3 (AJCC 9th) 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 QL1706 in induction chemotherapy and adjuvant chemotherapy. All patients will receive intensity-modulated radiotherapy (IMRT). QL1706 will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 9 cycles in adjuvant therapy.
Interventions
DRUGQL1706
QL1706 5mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
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
Qilu Pharmaceutical Co., Ltd.
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label
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. Tumor staged as T4N1 and T1-4N2-3 (AJCC 9th) * Stage II: T1-3N2 * Stage III: T1-4N3, T4N1-2 4. Eastern Cooperative Oncology Group performance score of 0-11. 5. Adequate marrow function: white blood cell count \> 4 × 10⁹/Lhemoglobin \>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 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. 9. 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) in intention-to-treat population | 3 years | Multiple endpoint 1: calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. |
| Overall survival (OS) in intention-to-treat population | 5 years | Multiple endpoint 2: calculated from randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) in per-protocol population | 3 years | calculated from randomization to the date of death from any cause. |
| Locoregional recurrence-free survival (LRRFS) | 3 years | calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence. |
| Distant metastasis-free survival (DMFS) | 3 years | calculated from randomization to the date of first distant metastasis. |
| Failure-free survival (FFS) in per-protocol population | 3 years | calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. |
| Quality of life (QoL) | week 1, 20, 40, 64 | 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. |
| 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 (III vs. IVA). |
| Tumor response | Every 6 weeks（the time of completion of induction chemotherapy, radiotherapy, and adjuvnt 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 |
| Adverse events (AEs) and serious adverse events (SAEs) | 3 years | Graded according to CTCAE V5.0. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Evaluate failure-free survival in the subgroup of clinical stage | 3 years | Subgroup analysis |
| Evaluate failure-free survival in the subgroup of plasma Epstein-Barr virus DNA level | 3 years | Subgroup analysis |
Countries
China
Contacts
Primary ContactJun Ma, M.D.
Backup ContactRui Guo, M.D.
Outcome results
None listed