Neoadjuvant PD-1 Blockade in Resectable Oral Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced oral squamous cell carcinoma.

Detailed Description
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The purpose of this study is to investigate the safety and feasibility of neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy in subjects with resectable local advanced OSCC. And on this basis, we will explore the changes of the profiles and functions of immune cells within tumors, lymph nodes and peripheral blood after the experimental interventions, as well as their correlation with the patients' response and prognosis.

Official Title
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A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma

Conditions
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Oral Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Camrelizumab
* Drug: Camrelizumanb plus TPF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented oral squamous cell carcinoma (biopsy required). Local advanced oral squamous cell carcinoma (clinical stage T1-2N1-3M0, T3-4aN0-3M0) with resection option for potential cure, as assessed by a faculty surgeon at Hospital of Stomatology, Wuhan University. Distant metastasis is excluded by chest CT and emission computed tomograph. Adequate organ function as follows: 1) Leukocyte count ≥ 2,000/mm3; 2) Absolute neutrophil count ≥ 1,000/mm3; 3) Platelet count ≥ 100,000/mm3; 4) Hemoglobin ≥ 90 g/L; 5) Serum albumin ≥30 g/L; 6) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); 7) AST (SGOT) and ALT (SGPT) < 2.5 × ULN; 8) ALP ≤ 2.5 × ULN; 9) Prothrombin time-international normalized ratio ≤ 1.5; 10) Serum creatinine ≤ 1.5 × ULN; 11) INR/PT≤ 1.5; 12) TSH ≤ ULN. ECOG performance status 0-1. Female patient tested HCG negative in serum or urine within 7 days prior to the start of investigational product. Both patient and partner must agree to use contraception prior to study entry and for the duration of study participation and for up to 120 days after the last dose of PD-1 blockade. Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Exclusion Criteria: History of ≥ 3 grade immune related adverse events (irAEs) or have not recovered to ≤ 1 grade irAEs from previous treatment. History of other treatments for cancer, including surgery, chemotherapy, radiotherapy or molecular targeted therapy within past 5 years. Previous therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 or any other antibody targeting T cell co-regulatory pathways. Active autoimmune disease or history of refractory autoimmune disease. Active systemic infection requiring therapy. Patients who are receiving psychotropic drug or alcohol/drug abuse. Subjects with concurrent other active malignancies. HIV or untreated active HBV or HCV infections, or vaccinated (HBV, flu, varicella, etc) within 4 weeks before recruitment. Uncontrollable systemic diseases, including diabetes, hypertension, etc. History of stroke or transient ischemic attack within past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant PD-1 blockade alone<br>The participants will receive 3 doses of neoadjuvant PD-1 blockade. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary. | Drug: Camrelizumab<br>* The participants will receive camrelizumab (200 mg) intravenous infusion each 2-week cycle for 3 cycles prior to surgery.<br>* Other names: SHR-1210;|
| Experimental: Neoadjuvant PD-1 blockade plus TPF induction chemotherapy<br>The participants will receive 3 doses of PD-1 blockade and 2 courses of TPF induction chemotherapy. Then the participants will take a radical surgery followed by radiotherapy or chemoradiotherapy if necessary. | Drug: Camrelizumanb plus TPF<br>* The participants will receive camrelizumab (200 mg) through intravenous infusion each 2-week cycle, and docetaxel (T) 75 mg/m2, cisplatin (P) 75 mg/m2, 5-Fluorouracil (F) 750 mg/m2 through intravenous infusion each 3-week cycle for 2 cycles.<br>* Other names: Docetaxel, Cisplatin, 5-Fluorouracil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic response. | Pathologic response of resected tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resected specimen. | 8 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic response. | Clinical response of tumors and lymph nodes to neoadjuvant PD-1 blockade alone or neoadjuvant PD-1 blockade plus TPF induction chemotherapy, as evaluated by radiographic examinations and defined by RECIST 1.1. | 8 weeks. | 
| Event-free survival (EFS) rate on each treatment arm. | EFS is the time from the date of randomization to the date of first record of disease progression as defined by RECIST 1.1. | 24 months. | 
| Overall survival (OS) on each treatment arm. | OS is the time from randomization to death due to any cause. | 24 months. | 
| Adverse events (AEs). | Number of participants experiencing any sign, symptom, disease, or worsening of preexisting conditions temporally associated with the experimental interventions or irrespective of the experimental interventions. | 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neoadjuvant, Oral squamous cell carcinoma, PD-1 blockade, Camrelizumab, TPF induction chemotherapy