Neoadjuvant Radiotherapy Combined With Toripalimab for Locally Advanced Head and Neck Squamous Cell Carcinoma

Study Overview
=================
Brief Summary
-----------------
This is a phase II study. Twenty-three patients with locally advanced head and neck squamous cell carcinoma were planned to be enrolled to assess the efficacy and safety of neoadjuvant immunotherapy combined with radiotherapy.

Detailed Description
-----------------
After receiving one cycle of immunotherapy, the subjects underwent SBRT radiotherapy to the lesion, followed by another cycle of immunotherapy. Surgery was performed 3-6 weeks later, and subsequent radiotherapy or chemoradiotherapy was decided after surgery based on pathological examination. Immunotherapy was maintained for 6 months. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of consent, or study termination by the principal investigator, whichever occurred first.

Official Title
-----------------
A Prospective Phase II Trial to Evaluate the Safety and Efficacy of Neoadjuvant Radiotherapy Combined With Immunotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Conditions
-----------------
Locally Advanced Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: Toripalimab
* Radiation: Stereotactic Body Radiation Therapy (SBRT)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sign informed consent; Age ≥ 18 years, regardless of gender; Histology or cytology confirmed head and neck squamous cell carcinoma, HNSCC (Oral cavity, oropharynx, larynx and hypopharynx), and previously untreated; Imaging confirmed that HNSCC was locally advanced and operable; Imaging confirmed no metastasis; ECOG physical status score 0-1; Life expectancy at least 24 weeks; Have measurable lesions; Good function of other major organs (liver, kidney, blood system, etc.): Absolute neutrophil count ((ANC) ≥ 1.0×10^9), platelet (≥ 80×10^9), hemoglobin (≥ 80g/L). Blood biochemical examination must meet: serum creatinine (Cr) ≤1.5 times the upper limit of normal (ULN) or endogenous creatinine clearance ≥60mL/min; TBIL≤1.5×ULN; ALB≥30g/L; ALT and AST≤ 3.0×ULN; TSH≤1.5×ULN; Female patients with fertility must undergo a pregnancy test (serum or urine) within 14 days before enrollment, and the result is negative, and they voluntarily adopt appropriate methods of contraception during the observation period and within 120 days after the last administration; Male patients must voluntarily take effective contraceptive measures from the start of treatment until 120 days after the last administration. Exclusion Criteria: Pregnant or breastfeeding, or planning to become pregnant during the study period Patients with active autoimmune diseases or immunodeficiency diseases, including but not limited to myasthenia gravis, interstitial pneumonia, enteritis, autoimmune hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, positive HIV test or a history of the above diseases, or a history of organ transplantation; Receiving systemic immunosuppressive drugs within 2 weeks before starting study treatment, or anticipating the need for systemic immunosuppressive drugs during study treatment; Received systemic immunostimulants (including but not limited to interferon or interleukin-2 [IL-2]) within 4 weeks before starting study treatment; History of other malignant tumors within the past 5 years, except cured cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ; Serious cardiovascular disease, unstable arrhythmia, or unstable angina pectoris within 3 months before starting study treatment; The subject has an active infection or infectious disease, or unexplained fever (body temperature > 38.5℃) during screening and before the first dose; Patients who have received therapeutic oral or intravenous antibiotics within 2 weeks prior to starting study treatment; patients receiving prophylactic antibiotic therapy (e.g., prophylaxis for urinary tract infection or chronic obstructive pulmonary - Untreated active hepatitis; Receiving immunotherapy such as PD-1/L1 antibody or CTLA-4 antibody within 4 weeks before enrollment; Received chemotherapy or targeted therapy within 4 weeks before enrollment; The subject has participated in or completed other clinical trials within 4 weeks before enrollment; Subjects may need to receive other anti-tumor therapy during the study; Subjects may need to receive a vaccine during the study or within 4 weeks prior to enrollment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental arm<br>Toripalimab + SBRT radiotherapy | Drug: Toripalimab<br>* 240mg, Q3W，I.V., D1, 2 cycles (1cycle of toripalimab before and after the SBRT radiotherapy, respectively), followed by the maintenance of toripalimab for 6 months after the surgery.<br>Radiation: Stereotactic Body Radiation Therapy (SBRT)<br>* Subjects were treated with SBRT radiotherapy (8Gy*5Fx), after 1 cycle of immunotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major pathological response (MPR) | Percentage of Participants with MPR. MPR is defined as > 90 percent decrease in viable tumor. | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) | Percentage of Participants with pCR. pCR is defined as the absence of residual tumor in both primary tumor and lymph nodes after neoadjuvant treatment. | up to 6 months | 
| Frequency and severity of perioperative adverse events | Grade 2-5 AEs according to NCI-CTCAE V5.0 | up to 6 months | 
| Quality of life questionnaires | EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) | up to 1 year |