Induction Chemoimmunotherapy Followed by Deescalated Definitive Radiotherapy in Head and Neck Cancer

NCT07791602 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: IDEAL-RT
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 6

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.

Conditions

Head and Neck Squamous Cell Carcinoma; Locally Advanced Head and Neck Cancer; HNSCC

Keywords

Induction Chemoimmunotherapy; De-escalated Radiotherapy; Camrelizumab; PD-1 Inhibitor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) at 2 year

  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.

  2 years after randomization

Secondary Outcomes (4)

• 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.

Other Outcomes (2)

• Change in Quality of Life (QoL)

  Baseline, end of radiotherapy, and every 3 months during follow-up (up to 2 years)

• MDADI swallowing function scale score

  Baseline, end of radiotherapy, and every 3 months during follow-up (up to 2 years)

Study Arms (2)

De-escalated Radiotherapy

EXPERIMENTAL

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.

Drug: Camrelizumab; Drug: Platinum-based Chemotherapy plus PD-1 inhibitor; Radiation: De-escalated Radiotherapy

Standard Radiotherapy

ACTIVE COMPARATOR

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.

Drug: Camrelizumab; Drug: Platinum-based Chemotherapy plus PD-1 inhibitor; Radiation: Standard Radiotherapy

Interventions

Camrelizumab DRUG

Camrelizumab 200 mg IV every 3 weeks for 8 cycles after radiotherapy as maintenance.

De-escalated Radiotherapy; Standard Radiotherapy

Platinum-based Chemotherapy plus PD-1 inhibitor DRUG

Cisplatin or carboplatin based chemotherapy combined with PD-1 inhibitor for 2-3 cycles as induction therapy.

De-escalated Radiotherapy; Standard Radiotherapy

De-escalated Radiotherapy RADIATION

Total dose 60 Gy to GTV (post-induction residual) in 25 fractions; CTV1 50 Gy/25 fractions; CTV2 45 Gy/25 fractions.

De-escalated Radiotherapy

Standard Radiotherapy RADIATION

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.

Standard Radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. 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.
• \. Willing to sign informed consent and comply with follow-up.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (6)

Air Force Medical Center

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Harbin Medical University Cancer Hospital

Harbin, China

Location

Cancer Hospital of Dalian University of Technology （Liaoning Cancer Hospital & Institute）

Shenyang, China

Location

Shanxi Cancer Hospital

Taiyuan, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, China

Location

Related Publications (5)

• Darragh LB, Karam SD. Radiation as an immune modulator: mechanisms and implications for combination with immunotherapy. Nat Rev Cancer. 2026 Apr;26(4):270-284. doi: 10.1038/s41568-025-00903-x. Epub 2026 Jan 23.

  PMID: 41577962 BACKGROUND

• Wu D, Li Y, Xu P, Fang Q, Cao F, Lin H, Li Y, Su Y, Lu L, Chen L, Li Y, Zhao Z, Hong X, Li G, Tian Y, Sun J, Yan H, Fan Y, Zhang X, Li Z, Liu X. Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial. Nat Commun. 2024 Mar 11;15(1):2177. doi: 10.1038/s41467-024-46444-z.

  PMID: 38467604 BACKGROUND

• Gong H, Tian S, Ding H, Tao L, Wang L, Wang J, Wang T, Yuan X, Heng Y, Zhang M, Shi Y, Xu C, Wu C, Wang S, Zhou L. Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial. Nat Commun. 2024 Jun 19;15(1):5251. doi: 10.1038/s41467-024-49121-3.

  PMID: 38898018 BACKGROUND

• Rosenberg AJ, Juloori A, Jelinek MJ, Agrawal N, Cursio JF, Cipriani N, Lingen MW, Izumchenko E, Katipally R, Chin J, Ginat D, Pasternak-Wise O, Gooi Z, Blair E, Pearson AT, Haraf DJ, Vokes EE. Neoadjuvant Nivolumab Plus Chemotherapy Followed by Response-Stratified Chemoradiation Therapy in HPV-Negative Head and Neck Cancer: The DEPEND Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2025 May 1;11(5):492-501. doi: 10.1001/jamaoncol.2025.0081.

  PMID: 40048190 BACKGROUND

• Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023 Aug;20(8):543-557. doi: 10.1038/s41571-023-00782-x. Epub 2023 Jun 6.

  PMID: 37280366 BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms

Interventions

camrelizumab; Platinum Compounds; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Inorganic Chemicals; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Jingbo Wang

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: August 28, 2026
• Study Start: June 12, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): December 1, 2032
• Last Updated: August 28, 2026

Record last verified: 2026-05

Locations

CN (6)