Head and Neck Squamous Cell Carcinoma
Conditions
Keywords
Head and Neck Cancer, Neoadjuvant therapy, Immunotherapy, EGFR-TKI, Chemotherapy
Brief summary
To explore the efficiency and safety of TP chemotherapy, tislelizumab, combined with afatinib as a new neoadjuvant treatment regimen for patients with resectable HNSCC.
Detailed description
More than 60% of patients with Head and neck squamous cell carcinoma (HNSCC) have locally advanced or metastatic disease at the time of diagnosis, with a 5-year overall survival rate of less than 60%. The clinical outcomes of those patients still need to be improved. Neoadjuvant therapy theoretically could reduce tumor volume, increase organ retention rate, and improve clinical prognosis. However, results from several phase III clinical trials have not proved a significant survival benefit of neoadjuvant chemotherapy for patients with resectable HNSCC except for nasopharyngeal carcinoma. There is an urgent need to explore new neoadjuvant treatment options for those patients. Immunotherapy such as PD-1/PD-L1 inhibitors have shown excellent efficiency in the treatment of malignancies. Anti-PD-1 therapy is approved as the first-line treatment of recurrent/metastatic HNSCC. Neoadjuvant immunotherapy for the treatment of locally advanced and resectable HNSCC has been demonstrated to be feasible in some trials. Afatinib, as an irreversible ErbB tyrosine kinase inhibitor (TKI), has been used as the second-line treatment for recurrent and/or metastatic HNSCC. A previous study published in 2018 confirmed that afatinib can be administered safely before surgery. In summary, we designed this study to explore the efficiency and safety of chemotherapy (TP regimen), anti-PD1 immunotherapy (tislelizumab), combined with EGFR-TKI (afatinib) as a new neoadjuvant treatment regimen for patients with resectable HNSCC, aiming to provide a new treatment option for those patients.
Interventions
DRUGNab-paclitaxel
260mg/m\^2 IV Q3W
DRUGCisplatin
75mg/m\^2 IV Q3W
BIOLOGICALTislelizumab
200mg IV Q3W
DRUGAfatinib
30mg PO QD
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 conditions: * 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: * anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； * antitumor vaccine; * any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; * 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 |
|---|---|---|
| Pathologic Complete Response | Time of surgery | Pathologic complete response was defined as the absence of viable tumor cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Major Pathologic Response | Time of surgery | Major pathologic response was defined as fewer than 10% viable tumor cells. |
| Objective Response Rate | Up to 8 weeks | Objective response rate was defined as the percentage of participants with a best overall response of CR or PR using RECIST Criteria |
| Adverse Events | Up to 12 weeks | Adverse events included adverse events using CTCAE Criteria and unplanned surgery delays. |
| Disease-free Survival | 1 year | Disease-free survival was defined as the time from the administration of the first dose to first disease progression or death. |
| Overall Survival | 1 year | Overall survival was defined as the time from the administration of the first dose to death. |
Countries
China
Outcome results
None listed