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

Study Overview
=================
Brief 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

Detailed Description
-----------------
The investigatorsdesigned a multi-center, single-arm, small sample clinical pilot study. In the clinical trial, patients were given regimes of induction therapy with PLPF (Pembrolizumab + Low dose- P (Platinum) F (5-Fluorouracil)): 6 cycles of Pembrolizumab treatment. Herein, the investigators describe eight consecutive unselected LA SCCHN (Locally Advanced Head and Neck Squamous Cell Carcinoma) patients based on 6 completed cycles of PLPF induction therapy.

Official Title
-----------------
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

Conditions
-----------------
Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
-----------------
* Drug: pembrolizumab+cisplatin + 5-FU


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years old, ≤ 85 years old Histologically or cytologically proven squamous cell carcinoma of the head and neck(except T4b stage patients) Primary tumor sites eligible: oral cavity, oropharynx, hypopharynx. (Although they are admittedly of squamous cell types, the following tumors will be excluded because of the Y responsiveness to chemotherapy: tumors of the nasal and paranasal cavities, larynx and of the nasopharynx.) At least one measurable lesion. No previous chemotherapy, radiotherapy or surgery (other than biopsy) for SSCHN. ECOG performance status of 0 or 1. No active autoimmune disease No concurrent malignancy Life expectancy of greater than 12 weeks. Adequate bone marrow, hepatic and renal functions. Available for treatment and follow-up. Exclusion Criteria: Multiple organs failure. distant metastases HNSCC. HPV p16 positive oropharyngeal cancer T4B advanced head and neck squamous cell carcinoma Current severe, uncontrolled systemic disease. Hepatitis B or active hepatitis C Mental illness. Peripheral neuropathy with CTCAE V5.0 ≥ level 2. History of severe (Grade 3 or 4) allergic or hypersensitivity reaction to therapeutic antibodies that required discontinuation of therapy. Malignancies other than SCCHN within 5 years prior to enrollment. Nasopharyngeal cancer. Pregnant or lactating women.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab+cisplatin + 5-fluorouracil<br>Use pembrolizumab+cisplatin + 5-fluorouracil | Drug: pembrolizumab+cisplatin + 5-FU<br>* ivgtt, pembrolizumab 200mg d1+cisplatin20 mg/m2 qd d1-d3 + 5-fluorouracil 3000mg/m last for 120hours , six circles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary site CR rate after neoadjuvant therapy | Measure the primary site CR rate after neoadjuvant therapy | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pfs | progression-free survival of all patients | up to 2 years | 
| dfs | disease free survival of all patients | up to 2 years | 
| Descending stage of tumor | Descending stage of primary lesion | up to 6 months | 
| One year local control rate | One year local control rate | up to 6 months | 
| Incidence of adverse reactions | safety of neoadjuvant therapy | up to 2 years | 
| OS | survival rates | 2 years | 
| Primary site pCR rate after neoadjuvant therapy | Primary site pCR rate after neoadjuvant therapy | Up to 6 months |