Toripalimab Versus Placebo Combined With Induction Chemotherapy Followed by Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma: a Multicenter, Randomized, Placebo-controlled, Double-blind, Phase 3 Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 466
- 试验地点
- 10
- 主要终点
- Progression-free Survival
研究概览
简要总结
The main questions it aims to answer are:
- Does the combination of GP induction chemotherapy and toripalimab improve the 3-year progression-free survival (PFS) compared to GP induction chemotherapy with placebo?
- What are the differences in CR after induction therapy, 3-year overall survival (OS), locoregional progression, and distant progression between the two groups?
- What are the differences in safety between the two groups?
- Are there predictive biomarkers of therapeutic efficacy, such as changes in EBV DNA or immune parameters, that correlate with treatment outcomes?
Researchers will compare the GP + toripalimab group with the GP + placebo group to see if the toripalimab combination shows superior efficacy.
Participants will:
Receive either GP chemotherapy with toripalimab or GP chemotherapy with placebo as induction therapy.
Undergo concurrent chemoradiotherapy ± adjuvant metronomic capecitabine following induction therapy.
Be monitored closely for safety and efficacy outcomes.
详细描述
Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Gemcitabine plus cisplatin (GP) has been demonstrated an effective chemotherapy regimen for NPC patients in previous studies. The results of GP combined with concurrent chemoradiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma showed 10% of locoregionally advanced NPC patients had complete response after three cycles of GP induction chemotherapy, and GP induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival (85.3% vs 76.5%) and overall survival (94.6% vs 90.3%) among locoregionally advanced NPC patients , as compared with chemoradiotherapy alone. Therefore, GP regimen has been established as the highest level of evidence-based induction chemotherapy in the 2020 National Comprehensive Cancer Network (NCCN) guidelines. Despite this intensified treatment approach, 20-30% of patients still have disease recurrences, highlighting the need for novel treatments in this population. Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma. So we hypothesize that GP induction chemotherapy combined with toripalimab could further improve survival of patients with locoregionally advanced NPC. The goal of this randomized, double-blind, controlled phase III clinical trial is to evaluate the efficacy and safety of the GP induction chemotherapy combined with toripalimab or placebo , followed by concurrent chemoradiotherapy ± adjuvant metronomic capecitabine in patients with high-risk locoregionally advanced nasopharyngeal carcinoma.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily participates and signs an informed consent form.
- •Aged 18-70 years, male or non-pregnant female.
- •Pathologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated, i.e., WHO Type II or III).
- •Staging of any T, N2-3 or T4N1 (9th AJCC/UICC staging), with no distant metastasis.
- •ECOG performance status score of 0-
- •Hemoglobin (HGB) ≥90 g/L, neutrocyte count≥1.5×10⁹/L, platelets (PLT) ≥100×10⁹ /L.
- •Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5×upper limit of normal (ULN), and bilirubin ≤ 1.5×ULN.
- •Adequate renal function: creatinine clearance rate ≥ 60 ml/min (Cockcroft-Gault formula).
- •Women of childbearing potential (WOCBP) who are sexually active must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug. Men who are sexually active with WOCBP must be willing to adhere to effective contraception during treatment and for 1 year after the last dose of the study drug.
排除标准
- •Age > 70 years or < 18 years.
- •Patients with recurrence or distant metastases.
- •Pathologically confirmed nasopharyngeal keratinizing squamous cell carcinoma (WHO Type I).
- •Patients who have previously undergone radiotherapy or systemic chemotherapy.
- •Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1000 copies/ml or 200IU/ml.
- •Hepatitis C virus (HCV) antibody positive.
- •Has active autoimmune disease, except type I diabetes, hypothyroidism treated with replacement therapy, and skin disease that doesn't require systemic treatment (e.g., vitiligo, psoriasis, or alopecia).
- •Has any condition that required systemic corticosteroid (equivalent to prednisone >10mg/d) or other immunosuppressive therapy within 28 days before informed consent. Patients who received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroids will be allowed.
- •Has a known history of active bacillus tuberculosis within 1 year; patients with adequately treated active bacillus tuberculosis over 1 year ago will be allowed.
- •Has a known history of interstitial lung disease.
- •Has received a live vaccine within 30 days before informed consent or will receive a live vaccine in the near future.
- •Is pregnant or breastfeeding.
- •Prior malignancy within 5 years, except in situ cancer, adequately treated non-melanoma skin cancer and papillary thyroid carcinoma.
- •Has known allergy to large molecule protein products or any compound of toripalimab.
- •Has a known history of human immunodeficiency virus infection.
- •Any other condition, including symptomatic heart failure, unstable angina, myocardial infarction, active infection requiring systemic therapy, mental illness, or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study or interferes with the interpretation of the results.
研究组 & 干预措施
Induction GP+placebo group
GP + Placebo Induction Therapy:
Gemcitabine: 1000 mg/m² on days 1 and 8 DDP (cisplatin): 80 mg/m² on day 1 Placebo: 240 mg on day 1 Total of 3 cycles.
Concurrent Chemoradiotherapy (CCRT):
DDP (cisplatin): 100 mg/m² on day 1 of radiation, then every 3 weeks during radiotherapy.
Total of 3 cycles (administered on D1, D22, and D43).
Adjuvant Metronomic Capecitabine Therapy:
Starts 4-6 weeks after the completion of radiotherapy and continues for up to 1 year.
Adjuvant metronomi capecitabine is administered at the physician's discretion: Capecitabine: 650 mg/m², administered BID (twice daily).
干预措施: GP plus placebo induction therapy (Drug)
Induction GP+toripalimab group
Induction GP + Toripalimab Therapy:
Gemcitabine: 1000 mg/m² on days 1 and 8 DDP (cisplatin): 80 mg/m² on day 1 Toripalimab: 240 mg on day 1 Total of 3 cycles.
Concurrent Chemoradiotherapy (CCRT):
DDP (cisplatin): 100 mg/m² on day 1 of radiation, then every 3 weeks during radiotherapy.
Total of 3 cycles (administered on D1, D22, and D43).
Adjuvant Metronomic Capecitabine Therapy:
Starts 4-6 weeks after the completion of radiotherapy and continues for up to 1 year.
Adjuvant metronomic capecitabine therapy is administered at the physician's discretion: Capecitabine: 650 mg/m², administered BID (twice daily).
干预措施: TORIPALIMAB INJECTION (JS001 ) combine with GP chemotherapy (Drug)
结局指标
主要结局
Progression-free Survival
时间窗: 3 years
Defined as the time from randomisation to first progression (locoregional or distant) or death, whichever occurred first.
次要结局
- Overall Survival(3 years)
- Locoregional Progression(3 years)
- Distant Progression(3 years)
- Complete Response Rate(9 weeks)
- Incidence of Acute and Late Toxicity(3 years)
研究者
Hai-Qiang Mai,MD,PhD
Professor
Sun Yat-sen University