Induction Chemotherapy and Toripalimab Followed by Radiotherapy in Unresectable Laryngeal/Hypopharyngeal Carcinoma

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to define whether combination of induction chemotherapy and PD-1 inhibitor (Toripalimab) followed by radiotherapy improve progression-free survival, for patients with unresectable laryngeal/hypopharyngeal carcinoma.

Detailed Description
-----------------
Historically, induction chemotherapy has been shown to increase laryngeal-preservation rate, improve disease-free survival and reduce the risk of distant metastasis. However, the prognosis of locally advanced laryngeal/ hypopharyngeal carcinoma remains poor. 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) followed by radiotherapy improve progression-free survival, for patients with unresectable laryngeal/hypopharyngeal carcinoma.

Official Title
-----------------
Induction Chemotherapy and Toripalimab Followed by Radiotherapy in Unresectable Laryngeal/Hypopharyngeal Carcinoma

Conditions
-----------------
Hypopharyngeal Cancer, Laryngeal Cancer

Intervention / Treatment
-----------------
* Drug: Toripalimab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Pathologically confirmed, unresectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma due to extensively local invasion or medical comorbidities (T3-4b, N0-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 and bone marrow 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 or 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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 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
Interventional Model Description: Induction chemotherapy with toripalimab, followed by cisplatin-based concurrent chemoradiation. At 3-6 weeks post-radiation, maintenance toripalimab was administered for 8 cycles.
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, followed by cisplatin-based concurrent chemoradiation. | Drug: Toripalimab<br>* Induction chemotherapy TP regimen combined with Toripalimab for 3 cycles: Toripalimab 240mg d1, Paclitaxel 175mg/m2 d2，Cisplatin 25mg/m2 d2-4 q3w. Then a total dose of 70Gy in 35 fractions was administered, with concurrently weekly cisplatin (30mg/m2 qw). At 3-6 weeks post-radiotherapy, maintenance Toripalimab was administered for 8 cycles (240mg d1 q3w, in total 8 cycles).<br>* Other names: JS001;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | From the rate of enrollment to first progression | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate of induction chemotherapy | Overall response rate of induction chemotherapy, evaluated by MR/CT imaging per RECIST 1.1 | up to 3 month | 
| Locoregional recurrence-free survival | From the rate of enrollment to first locoregional relapse | 2 year | 
| Distant metastasis-free survival | From the rate of enrollment to first distant metastasis | 2 year | 
| Overall survival | From the rate of enrollment to death | 2 year | 
| Laryngeal Preservation Rate | The incidence of those with partial/whole preservation of anatomic larynx, without evidence of local recurrence | 2 year | 
| Adverse Effect | Adverse Effect, evaluated by CTCAE 4.0.03 | up to 2 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Toripalimab, Induction chemotherapy, Immunotherapy, Radiotherapy