Induction Chemoimmunotherapy Followed by Deescalated Definitive Radiotherapy (IDEAL-RT) in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Multicenter, Prospective, Phase II, Randomized Non-Inferiority Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 180
- 试验地点
- 6
- 主要终点
- Progression-free Survival (PFS) at 2 year
研究概览
简要总结
This study aims to evaluate whether reducing the intensity of radiotherapy (de-escalated radiotherapy) after induction chemoimmunotherapy is not inferior to standard-dose radiotherapy in patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The study is a multicenter, prospective, phase II, randomized, non-inferiority controlled trial. A total of 180 participants who achieve deep tumor response (≥50% regression) after 2-3 cycles of induction chemotherapy plus PD-1 inhibitor (camrelizumab) will be randomized 1:1 to receive either de-escalated radiotherapy (experimental group) or standard radiotherapy (control group). Additional maintenance camrelizumab for 8 cycles after radiotherapy will be administered for both groups. The primary outcome is 2-year progression-free survival (PFS). Secondary outcomes include overall survival, local-regional control, distant metastasis-free survival, treatment-related adverse events, and quality of life. The study is expected to start in June 2026 and complete in December 2031.
详细描述
Background Induction chemoimmunotherapy has demonstrated marked response rates in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Conventional "expanded and escalated " radiotherapy to lymph node regions may reduce the systemic immune responses. Therefore, de-escalated radiotherapy after a good response to induction therapy may reduce accumulated toxicity while preserving efficacy and maintain the functional state of anti-tumor immune niche.
Objectives Primary: To determine if de-escalated radiotherapy is non-inferior to standard radiotherapy for 2-year PFS in LA-HNSCC patients with deep response (≥50% tumor regression) after induction chemoimmunotherapy.
Secondary: To compare overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), treatment-related adverse events (AEs, irAEs, SAEs), and quality of life (ECOG, EQ-5D-5L, MDADI) between the two groups.
Study Design Multicenter (8 sites in China), prospective, phase II, randomized (1:1), open-label, non-inferiority trial.
Eligibility Criteria:
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with head and neck squamous cell carcinoma (HNSCC) who have completed 2-3 cycles of induction chemotherapy plus PD-1 inhibitor and achieved deep response.
- •Within 1 month of achieving deep response, subsequent concurrent chemoradiotherapy is determined by integrating MDT recommendation and patient's discretion.
- •2. Age 18 to 75 years (including 75).
- •Histopathologically confirmed HNSCC (excluding nasopharyngeal carcinoma).
- •Clinical stage T1-2N2-3M0 or T3-4N0-3M0 (AJCC 8th edition).
- •HPV or P16 negative.
- •ECOG performance status 0 or
- •No contraindications to immunotherapy or radiotherapy.
- •Adequate organ function as defined by:
- •WBC ≥ 3.0×10^9/L, ANC ≥ 2.0×10^9/L, PLT ≥ 100×10^9/L, HGB ≥ 90 g/L (no transfusion or G-CSF within 14 days).
- •TBIL ≤ 2.0×ULN, ALT/AST ≤ 2.5×ULN, BUN/CRE ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min.
- •INR or PT ≤ 1.5×ULN (or within therapeutic range for anticoagulation).
- •Myocardial enzymes within normal limits.
- •For women of childbearing potential: negative pregnancy test within 7 days prior to enrollment and use of effective contraception during treatment and for 2 months after last dose. Male participants must agree to use effective contraception for the same period.
- •10. Willing to sign informed consent and comply with follow-up.
排除标准
- •Occurrence of ≥ G4 toxicities during induction therapy and not suitable to receiving subsequent concurrent chemoradiotherapy or immunotherapy.
- •History of another active malignancy within 5 years, except cured basal cell carcinoma of skin, cervical carcinoma in situ, papillary thyroid carcinoma, or superficial bladder cancer.
- •Active or history of autoimmune disease (e.g., interstitial pneumonia, uveitis, colitis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism/hypothyroidism requiring hormone replacement). Exceptions: vitiligo, childhood asthma fully resolved without intervention; asthma requiring bronchodilator medical intervention is excluded.
- •Uncontrolled cardiovascular disease: myocardial ischemia grade II or higher, myocardial infarction, poorly controlled arrhythmia (including QTc ≥ 470 ms), NYHA class III-IV heart failure, LVEF < 50%, or myocardial infarction within 1 year.
- •Active infection or unexplained fever >38.5°C during screening (tumor fever allowed if judged by investigator).
- •Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/mL), or active hepatitis C (HCV-RNA above lower limit of detection).
- •Prior treatment with any PD-1/PD-L1 inhibitor.
- •Allergy to cisplatin, macromolecular protein preparations, or any component of anti-PD-1 antibodies.
- •Major surgery for non-tumor reasons without full recovery of toxicity/complications before starting study treatment.
- •Pregnancy or breastfeeding.
- •Any other condition that, in the investigator's judgment, would interfere with study participation or data collection (e.g., severe psychiatric illness, abnormal laboratory values, family or social factors).
研究组 & 干预措施
De-escalated Radiotherapy
Participants receive de-escalated definitive radiotherapy after induction chemoimmunotherapy. Total dose 60 Gy to GTV (post-induction residual) in 25 fractions; CTV1 50 Gy/25 fractions; CTV2 45 Gy/25 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: Platinum-based Chemotherapy plus PD-1 inhibitor (Drug)
De-escalated Radiotherapy
Participants receive de-escalated definitive radiotherapy after induction chemoimmunotherapy. Total dose 60 Gy to GTV (post-induction residual) in 25 fractions; CTV1 50 Gy/25 fractions; CTV2 45 Gy/25 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: De-escalated Radiotherapy (Radiation)
Standard Radiotherapy
Participants receive standard definitive radiotherapy after induction chemoimmunotherapy. Total dose 69.96 Gy to GTV (post-induction residual) in 33 fractions; CTV1 60.06 Gy/33 fractions; CTV2 50.96 Gy/28 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: Platinum-based Chemotherapy plus PD-1 inhibitor (Drug)
Standard Radiotherapy
Participants receive standard definitive radiotherapy after induction chemoimmunotherapy. Total dose 69.96 Gy to GTV (post-induction residual) in 33 fractions; CTV1 60.06 Gy/33 fractions; CTV2 50.96 Gy/28 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: Standard Radiotherapy (Radiation)
De-escalated Radiotherapy
Participants receive de-escalated definitive radiotherapy after induction chemoimmunotherapy. Total dose 60 Gy to GTV (post-induction residual) in 25 fractions; CTV1 50 Gy/25 fractions; CTV2 45 Gy/25 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: Camrelizumab (Drug)
Standard Radiotherapy
Participants receive standard definitive radiotherapy after induction chemoimmunotherapy. Total dose 69.96 Gy to GTV (post-induction residual) in 33 fractions; CTV1 60.06 Gy/33 fractions; CTV2 50.96 Gy/28 fractions. Followed by camrelizumab maintenance 200 mg IV Q3W for 8 cycles.
干预措施: Camrelizumab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) at 2 year
时间窗: 2 years after randomization
PFS is defined as the time from randomization to the first documented disease progression (according to RECIST v1.1) or death from any cause, whichever occurs first. Participants who are alive and progression-free at 2 years will be censored.
次要结局
- Overall Survival (OS) at 2 year(2 years after randomization)
- Locoregional progression free survival (LRPFS) rate at 2 year(2 years after randomization)
- Distant Metastasis-Free Survival (DMFS) at 2 year(2 years after randomization)
- Incidence of Treatment-Related Adverse Events(From the start of radiotherapy until 90 days after last dose of camrelizumab.)