Induction Chemotherapy Combined With Toripalimab in Locoregionally-Advanced Laryngo-Hypopharyngeal Squamous Cell Cancer

Study Overview
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Brief Summary
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This is a non-randomized phase 1, open-labeled clinical study, 1-arm, single center, to observe efficacy and safety of chemotherapy plus PD-L1 antibody Toripalimab every 21 days for 2 cycles as induction regimen in locoregionally-advanced laryngo-hypopharyngeal squamous cell cancer patients.

Detailed Description
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Locoregionally advanced laryngo-hypopharyngeal squamous cell cancer patients have the demand of laryngo-preservation. Induction chemotherapy (FP) combined with Toripalimab (a humanized IgG4 monoclonal antibody against PD-1) will be given. This regimen will be given every 21 days for 2 cycles. Radiological examinations and PET(FDG/FAPI) examinations pre/post-treatment will be administrated for response evaluation.

Official Title
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Induction Chemotherapy Combined With Toripalimab in Locoregionally-Advanced Laryngo-Hypopharyngeal Squamous Cell Cancer

Conditions
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Locoregionally Advanced Laryngo-hypopharyngeal Squamous Cell Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil, Cisplatin, Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male/female patients aged≥18 years. Histologically confirmed Laryngo-hypopharyngeal squamous cell cancer, previously untreated (including surgery/radiotherapy/chemotherapy/immunotherapy). Locoregionally-advanced disease stage cT2-4N0-3M0. ECOG performance status 0 to 1. Adequate organ function: Absolute neutrophil count (ANC) ≥1.5x109/L, White blood count ≥3.5x109/L, Platelets ≥75x109/L, Hemoglobin (Hb) ≥70g/L, ALT/AST ≤2.5x ULN (for patient with liver metastasis ALT/AST ≤5x ULN), Serum bilirubin ≤1.5x ULN, Serum creatinine ≤1.5x ULN. HBV infected patients (inactive/asymptomatic carrier, chronic or active) with HBV DNA<500IU/ml (or 2500 copies/ml). Pregnancy test of female patients with fertile activity should be negative within 7 days before enrollment. Patients should keep contraception during treatment. Willingness and ability to comply with the protocol for the duration of the study including scheduled visits, examinations, investigations and treatment plans with informed consent form. Exclusion Criteria: Pregnancy or children bearing potential. Metastasis. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. Have other malignant tumors within 5 years, except for fully treated basal cell/squamous cell skin cancer/cervical cancer Uncontrolled clinical symptoms or diseases of the heart, such as: heart failure above NYHA II, unstable angina, myocardial infarction within 6 months; With uncontrolled auto-immune diseases, interstitial pneumonia, ulcerative colitis, or patients who should receive long-term glucocorticoid treatment (>10mg/d prednisone). With uncontrollable complications Inadequate organ function known hypersensitivity reaction to any of the study drugs or components. Other unsuitable conditions determined by investigators.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>5-Fluorouracil(750 mg/m2/d, CIV d1-5) Cisplatin(75mg/m2,d1)/Carboplatin(AUC5, d1) Toripalimab 240mg d1 | Drug: 5-Fluorouracil, Cisplatin, Toripalimab<br>* Drug: FP combined with Toripalimab Combination drugs: 5-Fluorouracil(F), Cisplatin/Carboplatin(P) and Toripalimab every 21 days for 2 cycles This is a single-arm study with all patients receiving these three drugs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response |  | 36 months | 
| Progression free survival rate at 12 months |  | 12 months | 
| Laryngo-preservation rate at 12 months |  | 12 months | 
| Overall survival rate at 24 months |  | 24 months | 
| Safety: adverse events as assessed by CTCAE v5. |  | 36 months |