A Randomized, Multicenter, Phase 3 Trial of Anlotinib Plus Immunochemoradiotherapy vs Immunochemoradiotherapy in High-Risk Locoregionally Advanced Nasopharyngeal Carcinoma
概览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- Sun Yat-sen University
- 入组人数
- 412
- 主要终点
- Failure-free survival (FFS)
概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤65 years
- •Patients with histologically confirmed non-keratinizing nasopharyngeal carcinoma according to WHO criteria.
- •Tumor staged as T4N2 and T1-4N3 (AJCC 9th)
- •Eastern Cooperative Oncology Group performance score of 0-
- •Adequate marrow function: white blood cell count \> 4 × 10⁹/L hemoglobin \>90g/L and platelet count \>100×10⁹/L
- •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
排除标准
- •listed in Item 8), additional assessments including myocardial function evaluation and cardiac ultrasound (echocardiography) must be performed, with results within normal limits
- •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.
- •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).
- •Exclusion Criteria
- •Positive for hepatitis B surface antigen (HBsAg) with hepatitis B virus DNA \>1×103 copies/mL, positive for anti-hepatitis C virus (HCV) antibody , positive for anti-hepatitis C virus (HCV) antibody
- •Positive for anti-HIV antibody or diagnosed with acquired immunodeficiency syndrome (AIDS).
- •Active pulmonary tuberculosis: Patients with a history of active tuberculosis within the past year should be excluded regardless of treatment status. Patients with a history of active pulmonary tuberculosis more than one year prior should also be excluded, unless they received confirmed and regular anti-tuberculosis treatment.
- •Active, known, or suspected autoimmune diseases, including but not limited to uveitis, colitis, hepatitis, hypophysitis, nephritis, vasculitis, systemic lupus erythematosus, hyperthyroidism, hypothyroidism, and asthma requiring bronchodilators. Type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia) are allowed.
- •History of interstitial lung disease or pneumonia requiring oral or intravenous corticosteroids within the past year; use of vancomycin within the past month.
- •Ongoing chronic systemic corticosteroid therapy (equivalent to or greater than prednisone \>10mg per day) or any other immunosuppressive therapy. Patients received inhale or topical corticosteroid are allowed.
研究组 & 干预措施
anlotinib hydrochloride Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Anlotinib Hydrochloride Capsules (Drug)
anlotinib hydrochloride Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Gemcitabine (GEM) (Drug)
anlotinib hydrochloride Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Cisplatin (Drug)
anlotinib hydrochloride Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Intensity-modulated radiotherapy (Radiation)
anlotinib hydrochloride Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Anlotinib hydrochloride (10mg, d1-d14) will be given every 3 weeks for 3 cycles in induction chemotherapy. Subsequently, adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Benmelstobart (Drug)
PD-L1+Chemoradiation Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Gemcitabine (GEM) (Drug)
PD-L1+Chemoradiation Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Cisplatin (Drug)
PD-L1+Chemoradiation Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Intensity-modulated radiotherapy (Radiation)
PD-L1+Chemoradiation Arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), and benmelstobart (1200mg, d1) every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. Adjuvant therapy with benmelstobart (1200 mg, d1) will be initiated for a total of 9 cycles.
干预措施: Benmelstobart (Drug)
结局指标
主要结局
Failure-free survival (FFS)
时间窗: 3 year
From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first
次要结局
- 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)
- Overall survival (OS)(3 years)
- Distant metastasis-free survival (DMFS)(3 years)
- Locoregional recurrence-free survival (LRRFS)(3 years)
- Adverse events (AEs) and serious adverse events (SAEs)(3 years)
- Quality of life (QoL)(week 1, 6, 24, 60, 72)
- Failure-free survival (FFS) within different subgroups(3 years)
研究者
Jun Ma, MD
Professor
Sun Yat-sen University