Head and Neck Squamous Cell Carcinoma, Locally Advanced Head and Neck Cancer, HNSCC
Conditions
Keywords
Induction Chemoimmunotherapy, De-escalated Radiotherapy, Camrelizumab, PD-1 Inhibitor
Brief summary
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.
Detailed description
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: * Age 18-75 years * Histologically confirmed HNSCC (non-nasopharyngeal), HPV/P16 negative * AJCC 8th stage T1-2N2-3M0 or T3-4N0-3M0 * ECOG 0-1 * Completed 2-3 cycles of induction chemotherapy (platinum-based) plus PD-1 inhibitor, achieving deep response (≥50% tumor reduction by RECIST) assessed by MDT * Adequate organ function * No prior immunotherapy Interventions: Induction (all patients) : 2-3 cycles of chemotherapy (cisplatin/carboplatin based) + PD-1 inhibitor. Randomization (1:1): * Experimental (de-escalated RT): GTV (post-induction residual): 60 Gy/25 fractions GTVtb (pre-induction tumor bed): not specified CTV1 (GTVtb + 1 cm): 50 Gy/25 fractions CTV2 (high-risk nodal stations + one station beyond): 45 Gy/25 fractions * Control (standard RT): GTV (post-induction residual): 69.96 Gy/33 fractions GTVtb (pre-induction tumor bed): not specified CTV1 (GTVtb + 1-1.5 cm + high-risk nodal stations): 60.06 Gy/33 fractions CTV2 (intermediate/low-risk nodal stations): 50.96 Gy/28 fractions * Maintenance: Camrelizumab 200 mg IV Q3W for 8 cycles Follow-up: Every 3 months for 2 years post-RT. Sample Size: 180 participants, 90 patients in each arm. Statistical Analysis: Baseline comparisons using Mann-Whitney U test; survival analysis using log-rank test and Cox regression; non-inferiority testing for PFS. Study Period: June 2026 (anticipated start) to December 2031 (completion). Ethics: Approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences (26/057-0382). Written informed consent will be obtained from all participants.
Interventions
DRUGCamrelizumab
Camrelizumab 200 mg IV every 3 weeks for 8 cycles after radiotherapy as maintenance.
DRUGPlatinum-based Chemotherapy plus PD-1 inhibitor
Cisplatin or carboplatin based chemotherapy combined with PD-1 inhibitor for 2-3 cycles as induction therapy.
RADIATIONDe-escalated Radiotherapy
Total dose 60 Gy to GTV (post-induction residual) in 25 fractions; CTV1 50 Gy/25 fractions; CTV2 45 Gy/25 fractions.
RADIATIONStandard Radiotherapy
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.
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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). 3. Histopathologically confirmed HNSCC (excluding nasopharyngeal carcinoma). 4. Clinical stage T1-2N2-3M0 or T3-4N0-3M0 (AJCC 8th edition). 5. HPV or P16 negative. 6. ECOG performance status 0 or 1. 7. No contraindications to immunotherapy or radiotherapy. 8. 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. 9. 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.
Exclusion criteria
1. Occurrence of ≥ G4 toxicities during induction therapy and not suitable to receiving subsequent concurrent chemoradiotherapy or immunotherapy. 2. 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. 3. 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. 4. 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. 5. Active infection or unexplained fever \>38.5°C during screening (tumor fever allowed if judged by investigator). 6. 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). 7. Prior treatment with any PD-1/PD-L1 inhibitor. 8. Allergy to cisplatin, macromolecular protein preparations, or any component of anti-PD-1 antibodies. 9. Major surgery for non-tumor reasons without full recovery of toxicity/complications before starting study treatment. 10. Pregnancy or breastfeeding. 11. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) at 2 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) at 2 year | 2 years after randomization | Time from randomization to death from any cause. Participants alive at 2 years will be censored. |
| Locoregional progression free survival (LRPFS) rate at 2 year | 2 years after randomization | LRPFS is defined as the time from randomization to the first documented local or regional 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. |
| Distant Metastasis-Free Survival (DMFS) at 2 year | 2 years after randomization | Time from randomization to first detection of distant metastasis or death, whichever occurs first. |
| Incidence of Treatment-Related Adverse Events | From the start of radiotherapy until 90 days after last dose of camrelizumab. | Percentage of participants with adverse events (AEs), immune-related AEs (irAEs), and serious AEs (SAEs) graded according to CTCAE v5.0. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJingbo Wang
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Outcome results
None listed