Nasopharyngeal Cancinoma (NPC), Nasopharyngeal Cancer
Conditions
Keywords
anlotinib hydrochloride, PD-L1 antibody, chemoradiotherapy
Brief summary
This trial aimed to evaluate the efficacy of anlotinib hydrochloride combined with benmelstobart, induction chemotherapy, and concurrent chemoradiotherapy (IC+CCRT), versus a regimen of benmelstobart plus IC+CCRT, in patients with high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC).
Detailed description
This trial will enroll patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) staged as T4N2 or T1-4N3 (AJCC 9th edition). Participants will be randomized 1:1 to either the control or experimental regimen. The control regimen consists of three cycles of induction chemotherapy (gemcitabine, cisplatin, and benmelstobart), followed by concurrent cisplatin-based chemoradiotherapy and 9 cycles of benmelstobart as adjuvant therapy. The experimental group will receive the same regimen plus anlotinib hydrochloride during the induction chemotherapy phase. All patients will receive intensity-modulated radiotherapy (IMRT). In the experimental group, anlotinib hydrochloride will be administered on days 1-14 of each 3-week induction cycle for three cycles.
Interventions
Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy.
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.
DRUGBenmelstobart
Benmelstobart 1200mg 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.
Sponsors
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 T4N2 and T1-4N3 (AJCC 9th) 4. Eastern Cooperative Oncology Group performance score of 0-11. 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 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) | 3 year | From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 62 weeks | Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians |
| Overall survival (OS) | 3 years | From date of randomization until the date of death from any cause, whichever came first |
| Distant metastasis-free survival (DMFS) | 3 years | From date of randomization until the date of first documented distant metastasis, whichever occurred first. |
| Locoregional recurrence-free survival (LRRFS) | 3 years | From date of randomization until the date of first documented locoregional recurrence, whichever occurred first. |
| 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. |
| 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. |
Contacts
CONTACTJun Ma, M.D.
CONTACTYa-Qin Wang, Ph. D.
PRINCIPAL_INVESTIGATORJun Ma, M.D.
Sun Yat-sen University
Outcome results
None listed