Cadonilimab as Induction-adjuvant PD-1/CTLA-4 Bispecific Blockade Combined With Induction Chenotherapy and Concurrent Chemoradiotherapy in High-risk Locoregionally-advanced Nasopharyngeal Carcinoma: a Multicenter, Randomized, Controlled, Multicenter, Phase 3 Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 490
- 试验地点
- 18
- 主要终点
- Failure-free survival (FFS) in intention-to-treat population
研究概览
简要总结
The trial aimed to compare cadonilimab combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in high-risk locoregionally-advanced nasopharyngeal carcinoma (LANPC).
详细描述
The trial plans to enroll patients with non-metastatic stage III-IVA (AJCC 8th, T4N1 or T1-4N2-3) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients were randomly assigned in a 1:1 ratio to receive either gemcitabine-cisplatin induction chemotherapy and concurrent chemoradiotherapy (standard-therapy group) or cadonilimab combined with standard therapy (cadonilimab group). Cadonilimab was administered at a dosage of 10 mg per square meter intravenously once every 3 weeks for up to 17 cycles (3 induction cycles and 14 adjuvant 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 (Outcomes Assessor)
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
- •Patients with histologically confirmed nasopharyngeal carcinoma.
- •Tumor staged as III-IVA (AJCC 8th, except T3N0-1 or T4N0).
- •Eastern Cooperative Oncology Group performance status ≤
- •Adequate marrow function: neutrocyte count≥1.5×10e9/L, hemoglobin ≥90g/L and platelet count ≥100×10e9/L.
- •Alanine Aminotransferase (ALT)/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).
- •Patients must be informed of the investigational nature of this study and give written informed consent.
- •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 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 > 65 or <
- •Hepatitis B surface antigen (HBsAg) positive and hepatitis B virus DNA >1×10e3 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 received systemic corticosteroid equivalent to prednisone ≤10mg/d, inhale or topical corticosteroid will be allowed.
- •Has a known history of active TB (bacillus tuberculosis) within 1 year; patients with adequately treated active TB 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 cadonilimab.
- •Has a known history of human immunodeficiency virus (HIV) 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
Cadonilimab arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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. Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
干预措施: Cadonilimab (Drug)
Cadonilimab arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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. Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
干预措施: Gemcitabine (Drug)
Cadonilimab arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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. Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
干预措施: Cisplatin (Drug)
Cadonilimab arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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. Cadonilimab 10mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 14 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
干预措施: Intensity-modulated radiotherapy (Radiation)
Chemoradiation arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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.
干预措施: Gemcitabine (Drug)
Chemoradiation arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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.
干预措施: Cisplatin (Drug)
Chemoradiation arm
Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 & 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), 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.
干预措施: Intensity-modulated radiotherapy (Radiation)
结局指标
主要结局
Failure-free survival (FFS) in intention-to-treat population
时间窗: 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
时间窗: 3 years
multiple endpoint 2: calculated from randomization to the date of death from any cause.
次要结局
- Failure-free survival (FFS) in per-protocol population(3 years)
- Overall survival (OS) in per-protocol population(3 years)
- Locoregional recurrence-free survival (LRRFS)(3 years)
- Distant metastasis-free survival (DMFS)(3 years)
- Adverse events (AEs) and serious adverse events (SAEs)(3 years)
- Quality of life (QoL)(week 1, 20, 40, 64)
- Failure-free survival (FFS) within different subgroups(3 years)
- Tumor response(Through study completion, an average of 1.2 year)
研究者
Jun Ma, MD
Professor
Sun Yat-sen University