Head and Neck Squamous Cell Carcinoma, Low-dose Radiotherapy, Immunotherapy, Targeted Therapy
Conditions
Brief summary
This study aimed to compare the efficacy of neoadjuvant low-dose radiotherapy combined with targeted therapy and immunotherapy versus targeted therapy and immunotherapy alone in patients with resectable head and neck squamous cell carcinoma.
Detailed description
Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor in the world. Due to its special anatomical location, HNSCC affects patients' appearance and physiological functions. Comprehensive treatments such as surgery, radiotherapy, and chemotherapy are often adopted. More than 60% of patients are diagnosed with locally advanced or metastatic diseases, resulting in a low 5-year survival rate. Locally advanced patients have high recurrence and metastasis rates and a poor prognosis. Neoadjuvant therapy before surgery theoretically can improve the possibility of radical surgery and the organ preservation rate. However, except for nasopharyngeal carcinoma, induction chemotherapy has not brought significant survival benefits to HNSCC patients, and new treatment regimens are urgently needed. EGFR is overexpressed in 90% of HNSCC patients. The PD-1/PD-L1 signaling pathway is an important mechanism of tumor escape. Anti-PD-1/PD-L1 monoclonal antibodies have shown good efficacy and high safety in the treatment of malignant tumors. The combination of radiotherapy and immunotherapy can induce an anti-tumor immune response. Low-dose radiotherapy has low toxicity and can reprogram the tumor immune microenvironment. Multiple studies have confirmed the safety and feasibility of its combination with immunotherapy. The previously conducted Prospective, Single-arm Clinical Study of Low-dose Radiotherapy Plus Tislelizumab Combined with Afatinib for Neoadjuvant Therapy of Resectable Head and Neck Squamous Cell Carcinoma has demonstrated good safety and efficacy. Based on this, a head-to-head clinical study is planned to compare the efficacy of low-dose radiotherapy combined with targeted therapy and immunotherapy and pure targeted therapy and immunotherapy in patients with resectable HNSCC, explore the clinical benefits of this new treatment measure, and provide new treatment options for HNSCC patients.
Interventions
DRUGTislelizumab
200mg ivgtt q3w
DRUGAfatinib
Targeted therapy
RADIATIONLow dose radiotherapy
Radiotherapy
Sponsors
West China Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age 18 years or above. 2. Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following condition: ①Were newly diagnosed and without distant metastasis; were deemed surgically resectable, evaluated by a head and neck surgeon; ②Were willing to undergo surgery; ③Eastern Cooperative Oncology Group (ECOG) performance status 0-1; ④Adequate organ and bone marrow function: Absolute neutrophil count ≥ 1.5 × 10\^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10\^9/L; ALT, AST and ALP \< 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN; albumin≥ 2.8 g/dL；Creatinine clearance ≥ 60 ml/min；INR≤ 1.5, APTT≤ 1.5×ULN. 3. Written informed consent.
Exclusion criteria
1. History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.） 2. Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease. 3. Any history of allergic disease, or a severe hypersensitivity reaction to drugs, or allergy to the study drug components. 4. Any of prior therapy with: ①anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； ②antitumor vaccine; ③any active vaccine against an infectious disease within 4 weeks before the first dose or planned during the study period; ④major surgery or serious trauma within 4 weeks before the first dose; ⑤toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 Grade 1 or the level specified by the inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response | Intraoperative | Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | Intraoperative | Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells. |
| Objective Response Rate | From the start of neoadjuvant therapy to the end of neoadjuvant therapy, the duration is approximately 2 months. | Objective Response Rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria. |
Countries
China
Contacts
Primary ContactXingchen Peng
Outcome results
None listed