An Open-label, Multicenter, Randomized Controlled Phase III Clinical Trial of PD-1 Monoclonal Antibody Plus Anlotinib Combined With Induction and Concurrent Chemoradiotherapy for High-risk Locoregionally Advanced Nasopharyngeal Carcinoma.
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 442
- 试验地点
- 1
- 主要终点
- 3-year progression-free survival
研究概览
简要总结
The investigators have designed a multicenter, open-label, randomized controlled phase III clinical study of GAPP induction therapy followed by concurrent chemoradiotherapy and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition). The aim is to obtain high-level, high-quality evidence-based data to clarify the efficacy and safety of combining chemoradiotherapy with PD-1 antibody and anlotinib, thereby providing a new treatment strategy to improve the prognosis of patients with high-risk locoregionally advanced nasopharyngeal carcinoma. In this study, GPP induction chemotherapy followed by concurrent chemoradiotherapy and toripalimab maintenance therapy is selected as the control group. This regimen is currently the standard treatment recommended by guidelines for high-risk locoregionally advanced nasopharyngeal carcinoma, with well-established efficacy and broad clinical application. It provides a reliable benchmark for comparing the efficacy and safety of the experimental group, meets ethical requirements, and has mature clinical operational procedures.
详细描述
The investigators have designed a multicenter, open-label, randomized controlled phase III clinical study of GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition). The aim is to obtain high-level, high-quality evidence-based data to clarify the efficacy and safety of combining chemoradiotherapy with PD-1 antibody and anlotinib, thereby providing a new treatment strategy to improve the prognosis of patients with high-risk locoregionally advanced nasopharyngeal carcinoma. In this study, GPP (gemcitabine + cisplatin + toripalimab) induction chemotherapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy is selected as the control group. This regimen is currently the standard treatment recommended by guidelines for high-risk locoregionally advanced nasopharyngeal carcinoma, with well-established efficacy and broad clinical application. It provides a reliable benchmark for comparing the efficacy and safety of the experimental group, meets ethical requirements, and has mature clinical operational procedures.
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
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
- •Voluntary participation and signed informed consent.
- •Age 18-65 years, male or non-pregnant female.
- •Pathologically confirmed non-keratinizing nasopharyngeal carcinoma (differentiated or undifferentiated type, i.e., WHO type II or III).
- •Previously untreated patients with no history of other malignancies; initial treatment for nasopharyngeal carcinoma.
- •Stage III: TanyN3M0 / T4N0-2M0 (9th AJCC/UICC staging system).
- •ECOG performance status 0-1, with no severe dysfunction of vital organs (heart, lung, liver, kidney, etc.).
- •Hemoglobin (HGB) ≥90 g/L, white blood cell count (WBC) ≥4.0×10^9 /L, platelet count (PLT) ≥100×10^9/L.
- •Liver function: ALT and AST <2.5× upper limit of normal (ULN); total bilirubin <2.0×ULN.
- •Renal function: serum creatinine <1.5×ULN.
排除标准
- •Patients with recurrent or distant metastatic nasopharyngeal carcinoma.
- •Pathologically confirmed keratinizing squamous cell carcinoma (WHO type I).
- •Receipt of systemic or topical glucocorticoid therapy within 4 weeks prior to enrollment.
- •Participation in another clinical trial of an investigational drug within 3 months prior to treatment.
- •Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
- •Patients with idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans), radiation pneumonitis that is clinically symptomatic or requires steroid therapy, active pneumonitis, or other moderate-to-severe pulmonary diseases that significantly affect lung function.
- •Comorbidities requiring long-term immunosuppressive medication or systemic/topical corticosteroids at immunosuppressive doses.
- •Prior use of anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibodies (or any other antibodies targeting T-cell co-stimulatory or checkpoint pathways) with documented disease progression at the time of study entry.
- •Presence of any active autoimmune disease or history of autoimmune disease (including but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, nephritis). Patients with vitiligo or childhood asthma that has completely resolved and requires no intervention in adulthood may be included; patients requiring bronchodilators for medical management of asthma are excluded.
- •HIV-positive; HBsAg-positive with detectable HBV DNA copy number (quantitative detection ≥1000 cps/mL); positive hepatitis C antibody (HCV Ab) with detectable HCV RNA.
- •Receipt of any anti-infective vaccine (e.g., influenza vaccine, varicella vaccine) within 4 weeks prior to enrollment.
- •Positive pregnancy test in women of childbearing potential, or lactating women.
- •Inability to comply with scheduled follow-up due to psychological, social, family, or geographical reasons.
研究组 & 干预措施
GAPP group
GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: radiation (Radiation)
GPP group
GPP (gemcitabine + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: radiation (Radiation)
GPP group
GPP (gemcitabine + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Cisplatin (Drug)
GAPP group
GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Toripalimab (Drug)
GAPP group
GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Anlotinib (Drug)
GAPP group
GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Cisplatin (Drug)
GAPP group
GAPP (gemcitabine + anlotinib + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Gemcitabine (Drug)
GPP group
GPP (gemcitabine + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Toripalimab (Drug)
GPP group
GPP (gemcitabine + cisplatin + toripalimab) induction therapy followed by concurrent chemoradiotherapy (cisplatin) and toripalimab maintenance therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (stage III, AJCC 9th edition)
干预措施: Gemcitabine (Drug)
结局指标
主要结局
3-year progression-free survival
时间窗: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
3-year progression-free survival
次要结局
未报告次要终点
研究者
YiJun Hua
Chief Physician
Sun Yat-sen University