Induction Chemotherapy and Toripalimab for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

Study Overview
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Brief Summary
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The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Detailed Description
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Historically, induction chemotherapy could provide a chance of larynx preservation for approximate 60-70% of patients with locally advanced laryngeal/hypopharyngeal carcinoma. Recently, phase I-II clinical studies demonstrated excellent pathological response of induction PD-1 inhibitor with/without chemotherapy for locally advanced head and neck cancer. The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) improve the rate of larynx preservation, for patients with resectable laryngeal/hypopharyngeal carcinoma.

Official Title
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Induction Chemotherapy and Toripalimab Followed by Surgery or Radiotherapy for Larynx Preservation in Resectable Laryngeal/Hypopharyngeal Carcinoma

Conditions
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Laryngeal Cancer, Hypopharynx Cancer, Laryngeal Neoplasms

Intervention / Treatment
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* Drug: chemotherapy TP regimen combined with Toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma (T2-4a, N0-resectable N3, M0); Age between 18-75 years; Signed inform consent; Had at least one measurable lesion according to RECIST 1.1 criteria Anticipated overall survival more than 3 months; Satisfactory performance status: ECOG (Eastern Cooperative Oncology Group) scale 0-1; Normal organ function; HBV DNA<500 IU/mL（or 2500 copies/mL）and HCV RNA negative ; Male and no pregnant female, able to adapt birth control methods during treatment. Exclusion Criteria: Hypersensitivity to Toripalimab, Paclitaxel, Nab-Paclitaxel and Cisplatin; Suffered from malignant tumors, except cervical carcinoma in situ, papillary thyroid carcinoma, or skin cancer (non- melanoma) within five years; Severe, uncontrolled heart disease; Receive vaccine or live vaccine within 28 days prior to signing the informed consent; Equivalent dose more than prednisone 10mg/d or other immunosuppressive treatments within 28 days prior to signing the informed consent; Surgery or trauma within 28 days prior to signing the informed consent; Received other immune checkpoint inhibitors previously; Severe, uncontrolled infections within 28 days of prior to signing the informed consent; Active, known or suspected autoimmune disease; Type I Diabetes, hypothyroidism those only need hormone replacement therapy, vitiligo or inactive asthma who don't need systemic therapy can recruit; History of interstitial lung disease; HIV positive; Hepatitis B surface antigen (HBsAg) positive and HBV-DNA ≥500IU/ml, or 2500cps/ml; Positive HCV RNA; Other diseases which may influence the safety or compliance of the clinical trial, such as mental illness, or their family and society factors; Women of child-bearing potential who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Induction chemotherapy and Toripalimab<br>Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2 or Nab-Paclitaxel 260mg/m2 d2，Cisplatin 25mg/m2 d2-4 q3w. Response rate of primary tumor is evaluated using laryngoscopy and head and neck MRI after 3 cycles of induction therapy. If ORR of primary tumor is CR/PR, then chemoradiation is conducted, followed by maintenance therapy of Toripalimab for 8 cycles (6 months). Otherwise, surgery is conducted (laryngeal preservation surgery is preferred), followed by adjuvant radiation/chemoradiation and then maintenance therapy of Toripalimab for 8 cycles. | Drug: chemotherapy TP regimen combined with Toripalimab<br>* Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2 or Nab-Paclitaxel 260mg/m2 d2，Cisplatin 25mg/m2 d2-4 q3w. Response rate of primary tumor is evaluated using laryngoscopy and head and neck MRI after 3 cycles of induction therapy. If overall response rate of primary tumor is complete response or partial response, then chemoradiation is conducted, followed by maintenance therapy of Toripalimab for 8 cycles (6 months). Otherwise, surgery is conducted (laryngeal preservation surgery is preferred), followed by adjuvant radiation/chemoradiation and then maintenance therapy of Toripalimab for 8 cycles.<br>* Other names: Cisplatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laryngeal Preservation rate at 3-month post-radiotherapy | defined as the absence of any residual disease that would justify salvage total laryngectomy | 3-month post-radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate of induction therapy | Overall response rate of induction therapy evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria | 2 weeks after the 3th cycle of induction therapy | 
| Overall response rate of treatment | Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria | 3 months post-radiotherapy | 
| Pathological complete response rate of the patients receiving surgical resection | Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists | Within 3 weeks after surgery | 
| Major pathologic response rate of the patients receiving surgical resection | Major pathologic response rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists. | Within 3 weeks after surgery | 
| Overall survival rate at 1 year | Overall survival rate at 1 year | One year post-radiotherapy | 
| Overall survival rate at 2 year | Overall survival rate at 2 year | Two year post-radiotherapy | 
| Progression-free survival rate at 1 year | Progression-free survival rate at 1 year | One year post-radiotherapy | 
| Progression-free survival rate at 2 year | Progression-free survival rate at 2 year | Two year post-radiotherapy | 
| Laryngeal Preservation rate at 1 year | Laryngeal Preservation rate at 1 year | One year post-radiotherapy | 
| Laryngeal Preservation rate at 2 year | Laryngeal Preservation rate at 2 year | Two year post-radiotherapy | 
| Adverse Effect | Adverse Effect, evaluated by CTCAE 4.0.03 | One year post-radiotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction chemotherapy, Checkpoint inhibitor, PD-1 inhibitor, Toripalimab, Larynx preservation