RecruitingPhase 2NCT05446467

Pembrolizumab in Combination With Low-dose PFas Neoadjuvant Treatment for Locally Advanced HNSCC

Safety and Efficacy of Pembrolizumab in Combination With Low-dose PF (Cisplatin and 5-Fluorouracil) as Neoadjuvant Treatment for Locally Advanced Head and Neck Squamous Cell Carcinoma: a Multi-center, Single-arm Clinical Study Trial

Sponsor

Zhejiang Provincial People's Hospital

Enrollment

80 participants

Start Date

Sep 1, 2022

Study Type

INTERVENTIONAL

Conditions

Head and Neck Squamous Cell Carcinoma

Summary

A phase Ⅱ open label multi-cencter clinical trail to evaluate the efficacy and safety of pembrolizumab combined with low-dose PF (cisplatin + 5-fluorouracil) in the neoadjuvant treatment of locally advanced head and neck squamous cell carcinoma

Eligibility

Min Age: 18 YearsMax Age: 85 Years

Inclusion Criteria15

Age ≥ 18 years old, ≤ 85 years old
Histologically or cytologically proven squamous cell carcinoma of the head and neck; Patients diagnosed with head and neck squamous cell carcinoma with stage III and IV A without distant metastasis according to AJCC staging (8th editon), including squamous cell carcinoma of oropharyngeal (P16-), oral cavity, hypopharyngeal and larynx
Measurable primary lesions per RECIST 1.1 criteria
Treatment-naive patients without any previous disease-related therapy (except for diagnostic biopsies on primary lesions)
ECOG performance status of 0 or 1
Selective standard surgery+ standard adjuvant chemo-radiotherapy/radiotherapy as judged by the investigator
No active autoimmune disease
No concurrent malignancy
Life expectancy is estimated to be over 3 months
Have sufficient tumour tissue samples available for CPS PD-L1 immunohistochemical examination (22C3 DAKO)
No abvious signs of hematological disorders, ANC≥1.5×109 /L, platelets ≥100×109 /L, Hb≥ 90 g/L,WBC ≥3.0×109 /L before enrollment, no blood transfusion and bleeding tendency within 7 days
ALT,AST and ALP ≤ 2.5 × upper limit of normal (ULN); Serum bilirubin ≤ 1.5 × ULN, for patients with known Gilbert disease, serum bilirubin ≤ 3 x ULN
Serum creatinine ≤1.5 or creatinine clearance\>50 mL/min
HPV status determined by p16 IHC, in situ hybridization, or by polymerase chain reaction-based assays
Able to understand this study, patient and (or) legal representative voluntarily agree to participate in this trial and sign informed consent

Exclusion Criteria19

Multiple organs failure
HPV p16 positive oropharyngeal cancer
Patients with local advanced head and neck squamous cell carcinoma stage T4B and/or N3
Patients with distant metastasis
Uncontrolled serious diseases that, as assessed by investigator, may affect the subject's treatment with the study protocol, such as serious heart disease, cerebrovascular disease, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc.
Diagnosis of dementia, altered mental status or any mental illness that would prevent subjects understanding or giving informed consent or completing questionnaires
Subjects with ≥ Grade 2 peripheral neuropathy according to CTCAE V5.0
Subjects with ≥ Grade 2 hearing impairment according to CTCAE V5.0
History of allergy or hypersensitivity to any of the therapeutic ingredients
Diagnosis of malignancy within 5 years prior to screening, including HNSCC (other than current HNSCC) and other malignancies; Eligibility is achieved if all of the following criteria are met: malignancies received curative therapy, such as adequately treated cervical carcinoma in situ, non-melanoma cutaneum carcinoma, localized prostate cancer after radical operation, breast ductal carcinoma in situ after radical operation; There was also no evidence of recurrence or metastasis based on imaging and tumor markers
Known history of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
Patients diagnosed with nasopharyngeal carcinoma or squamous cell carcinoma whose lesions are located in parts other than the oral cavity, oropharynx, larynx and hypopharynx (such as sinuses, paranasal sinuses and unknown primary site)
Participated in other clinical intervention trials or received other investigational therapies within 30 days prior to screening
Patients received systemic corticosteroids (prednisone equivalent dose\>10mg/day) or other immunosuppressive drugs within 14 days prior to randomization. If there is no active autoimmune disease, inhaled or topical steroid hormones and adrenal hormone replacement therapy with prednisone equivalent doses\>10mg per day are permitted
Pregnant or breastfeeding; Subjects of childbearing age refuse to accept contraceptive measures
Patients unfit for study as assessed by the investigator
Received systemic antibiotics within 1 weeks prior to first dose of study therapy or active infection requiring treatment
Known history of HBV infection (defined as HBsAg positive) or active HCV infection (defined as HCV RNA detected)
Has received live vaccine during study or within 30 days prior to first dose of study therapy

Interventions

COMBINATION_PRODUCTpembrolizumab+cisplatin + 5-FU

ivgtt, pembrolizumab 200mg d1+cisplatin20 mg/m2 qd d1-d3 + 5-fluorouracil 3000mg/m2 last for 120hours, six circles. Subjects will undergo surgery after receiving neoadjuvant chemotherapy within 3 weeks, followed by adjuvant therapy and pembrolizumab alone maintenance treatment.