Hypopharynx Cancer, Laryngeal Cancer, Laryngeal Neoplasms
Conditions
Keywords
Induction chemotherapy, Checkpoint inhibitor, PD-1 inhibitor, Toripalimab, Larynx preservation
Brief summary
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
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.
Interventions
DRUGchemotherapy TP regimen combined with Toripalimab
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.
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Laryngeal Preservation rate at 3-month post-radiotherapy | 3-month post-radiotherapy | defined as the absence of any residual disease that would justify salvage total laryngectomy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival rate at 1 year | One year post-radiotherapy | Overall survival rate at 1 year |
| Progression-free survival rate at 2 year | Two year post-radiotherapy | Progression-free survival rate at 2 year |
| Laryngeal Preservation rate at 1 year | One year post-radiotherapy | Laryngeal Preservation rate at 1 year |
| Laryngeal Preservation rate at 2 year | Two year post-radiotherapy | Laryngeal Preservation rate at 2 year |
| Adverse Effect | One year post-radiotherapy | Adverse Effect, evaluated by CTCAE 4.0.03 |
| Overall response rate of induction therapy | 2 weeks after the 3th cycle of induction therapy | Overall response rate of induction therapy evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria |
| Overall response rate of treatment | 3 months post-radiotherapy | Overall response rate of treatment evaluated by head and neck MR/CT, laryngoscopy using Recist 1.1 Criteria |
| Pathological complete response rate of the patients receiving surgical resection | Within 3 weeks after surgery | Pathological complete response rate of the patients receiving surgical resection, evaluated by experienced pathologists |
| Major pathologic response rate of the patients receiving surgical resection | Within 3 weeks after surgery | Major pathologic response rate, defined as no more than 10% of residual viable tumor, evaluated by experienced pathologists. |
| Overall survival rate at 2 year | Two year post-radiotherapy | Overall survival rate at 2 year |
| Progression-free survival rate at 1 year | One year post-radiotherapy | Progression-free survival rate at 1 year |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pathological complete response rate by different biomarker subgroups | Within 3 weeks after surgery | Experimental Biomarker Analysis: the relationship with different biomarkers and pathological complete response rate of the patients receiving surgical resection |
| Major pathologic response rate by different biomarker subgroups | Within 3 weeks after surgery | Experimental Biomarker Analysis: the relationship with different biomarkers and major pathologic response rate of the patients receiving surgical resection |
| Laryngeal Preservation rate at 3 month post-radiotherapy by different biomarker subgroups | 3-month post-radiotherapy | Experimental Biomarker Analysis: the relationship with different biomarkers and 3 month laryngeal preservation rate |
| Overall response rate of induction therapy, by different biomarker subgroups | 2 weeks after the 3th cycle of induction therapy | Experimental Biomarker Analysis: the relationship with different biomarkers and overall response rate of induction therapy |
Countries
China
Contacts
Primary ContactXiayun He, M.D.
Backup ContactYu Wang, M.D.
Outcome results
None listed