Head and Neck Cancer
Conditions
Keywords
Head and Neck Cancer, Neoadjuvant therapy, Immunotherapy, EGFR-TKI
Brief summary
The purpose of this study is to explore the efficiency and safety of anti-Programmed death-1 (PD-1) immunotherapy, tislelizumab, combined with EGFR-tyrosine kinase inhibitor (TKI), afatinib as a new neoadjuvant treatment regimen for patients with resectable head and neck squamous cell carcinoma (HNSCC).
Detailed description
Head and neck squamous cell carcinoma (HNSCC) is the most common malignancy of the head and neck. More than 60% of patients with 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 can reduce tumor volume, increase organ retention rate, and reduce distant metastasis rate. However, in addition to nasopharyngeal carcinoma, results from several phase III clinical trials have not proved a significant survival benefit of neoadjuvant chemotherapy for patients with resectable HNSCC. It is urgent to explore new neoadjuvant treatment options to improve the prognosis of patients with HNSCC. 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. However, there is a lack of high-level evidence-based medical evidence for the use of afatinib in preoperative therapy for HNSCC. A previous study published in 2018 confirmed that afatinib can be administered safely before surgery. In summary, the investigators designed this study to explore the efficiency and safety of 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
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 |
|---|---|---|
| Major Pathologic Response | Time of surgery | Major Pathologic Response (MPR) was defined as fewer than 10% viable tumor cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic Complete Response | Time of surgery | Pathologic Complete Response (pCR) was defined as the absence of viable tumor cells. |
| 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. |
| Adverse events | Up to 12 weeks | Adverse events were defined as the number of participants with adverse events using CTCAE Criteria or with an unplanned surgery delay. |
| 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. |
Countries
China
Outcome results
None listed