Iparomlimab and Tuvonralimab Combined With SFRT and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky HNSCC
brief summary
Study Objectives 1. Primary Objective: The core aim of this study is to investigate whether the sequential approach of Spatially Fractionated Radiotherapy followed by 3 cycles of induction chemotherapy combined with Iparomlimab and Tuvonralimab, definitive chemoradiotherapy, and maintenance therapy with the Iparomlimab and Tuvonralimab can improve the 2-year event-free survival (EFS) rate in patients with locoregionally advanced bulky head and neck squamous cell carcinoma (HNSCC). 2. Secondary Objectives:s To analyze the impact of this integrated treatment regimen on key efficacy endpoints, including: Objective response rate (ORR), Duration of response (DoR), Distant metastasis-free survival (DMFS), Local region recurrence-free survival (LRRFS), Overall survival (OS)。 2. Study Endpoints (1) Primary Endpoint and Definition: 2-Year Event-Free Survival (EFS) Rate (2) Secondary Endpoints and Definitions: 1. 2-Year Overall Survival (OS) Rate 2. 2-Year Distant Metastasis-Free Survival (DMFS) Rate. 3. 2-Year Local Region Recurrence-Free Survival (LRRFS) Rate. 4. Objective Response Rate (ORR). 5. Duration of Response (DoR). 6. Quality of Life (QoL): Assessed across multiple domains: Physical Function: Measured via tools like the 6-minute walk test or ADL (Activities of Daily Living) scale. Psychological Status: Evaluated using instruments such as HAMD (Hamilton Anxiety and Depression Scale) or MMSE (Mini-Mental State Examination). Social Function: Assessed via social engagement questionnaires (e.g., HAQ-DI \[Health Assessment Questionnaire-Disability Index\]). Spiritual Well-being: Evaluated using tools like PIL (Purpose in Life test). Clinically meaningful improvements in these domains before and after treatment define successful QoL endpoints (e.g., positive changes in physical, psychological, social, and spiritual health in cardiac patients). 7. Safety: The nature and severity of adverse reactions associated with the treatment. 8. Tolerability: The degree to which patients can endure treatment-related side effects.
detailed description
I. Study Design and Technical Route Details 1. Stratified Implementation of Treatment Protocols
1. Spatially Fractionated Radiotherapy (SFRT) Phase Technical Parameters: Three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT) is used to deliver a single high-dose fraction to the primary tumor and bulky metastatic lymph nodes (≥5 cm), with a prescribed dose of 10-20Gy/1 fraction. Dose-volume histogram (DVH) optimization ensures target coverage while limiting doses to organs at risk (e.g., spinal cord ≤45Gy, parotid gland mean dose ≤26Gy).
Timing: A positioning CT scan (slice thickness ≤3 mm) is completed within 7 days of enrollment. The radiation oncologist contours the target volumes, and the physicist designs the treatment plan, which is reviewed by a multidisciplinary team (MDT) before implementation. 2. Induction Chemotherapy Combined with Immunotherapy Phase
Drug Regimen:
Docetaxel: 75mg/m², intravenous drip, d1, Q3W for 3 cycles (body surface area calculated using measured height and weight, precise to 0.01m²).
Cisplatin: 25mg/m², intravenous drip, d1-3, Q3W for 3 cycles (hydration pretreatment required, daily fluid intake ≥2000ml, electrolyte monitoring).
Iparomlimab and Tuvonralimab: 5mg/kg, intravenous infusion, d1, Q3W for 3 cycles (diluted in 100ml 0.9% sodium chloride solution, infusion duration ≥30 minutes; electrocardiographic monitoring required for the first dose).
Cycle Transition: Induction therapy starts within 7 days after SFRT. Each chemotherapy cycle requires confirmation of normal blood counts (ANC ≥1.5×10⁹/L, PLT ≥90×10⁹/L) and liver/kidney function (ALT/AST ≤2.5×ULN) before initiation. 3. Definitive Concurrent Chemoradiotherapy Phase
Radiotherapy Protocol:
Target Volume Definition: GTVₜₙ₀ (primary tumor) receives 70Gy/30-33 fractions, GTVₙ (positive lymph nodes) receives 66-70Gy/30-33 fractions, and clinical target volume (CTV) receives 54-60Gy/30-33 fractions. IMRT is used with daily fractions (2Gy/fraction), total treatment time ≤6 weeks.
Concurrent Chemotherapy: Cisplatin 100mg/m², infused over 3 days (d1-3), Q3W for 2 cycles. Chemotherapy starts simultaneously with radiotherapy, within 48 hours of each other. 4. Immunotherapy Maintenance Phase Protocol: Iparomlimab and Tuvonralimab 5mg/kg, Q3W, intravenous infusion for 14 cycles (total treatment duration \~1 year).
official title
A Prospective, Single-Arm Clinical Trial of Iparomlimab and Tuvonralimab Combined With Spatially Fractionated Radiotherapy and Definitive Chemoradiotherapy in Locoregionally Advanced Bulky Head and Neck Squamous Cell Carcinoma