Head and Neck Cancer
Conditions
Brief summary
This study compares the efficacy of neoadjuvant low-dose radiotherapy plus targeted-immunotherapy versus targeted-immunotherapy alone in resectable HNSCC patients.
Detailed description
Head and neck squamous cell carcinoma (HNSCC) is a common malignant tumor in the head and neck region. It has a high global incidence. 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 (LDRT) 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. Based on this, a head-to-head clinical study is planned to compare the efficacy of low-dose radiotherapy combined with targeted immunotherapy and pure targeted immunotherapy in patients with resectable head and neck squamous cell carcinoma, explore the clinical benefits of this new treatment measure, and provide new treatment options for HNSCC patients.
Interventions
DRUGTislelizumab
200mg IV Q3W
DRUGAfatinib
30mg PO QD
RADIATIONLow dose radiotherapy
4Gy / 2f. Intensity-modulated radiotherapy was used for 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: ◦ were newly diagnosed and without distant metastasis; were deemed surgically * resectable evaluated by a head and neck surgeon; * were willing to undergo surgery. 3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1. 4. Adequate 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. 5. 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 sever hypersensitivity reaction to drugs, or allergy to the study drug components. 4. Any of prior therapy with: （1）anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； （2）antitumor vaccine; （3）any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; （4）major surgery or serious trauma within 4 weeks before the first dose; toxicity 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 |
|---|---|---|
| Objective Response Rate | Up to 8 weeks | Objective Response Rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria |
| Disease-free Survival | 1 year | Disease-free Survival (DFS) was defined as the time from the administration of the first dose to first disease progression or death. |
| Pathologic Complete Response | Intraoperative | Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells. |
| Overall Survival | 1 year | Overall Survival (OS) was defined as the time from the start of treatment initiation to the patient's death from any cause. |
| Immune microenvironment | Intraoperative | The local microenvironment of tumor cells, including the changes of T lymphocytes, B lymphocytes and other cells. |
| Progression-Free Survival | 1 year | Progression-Free Survival (PFS) was defined as the time from the commencement of therapy to the first evidence of disease progression or death. |
Outcome results
None listed