Hypopharyngeal Cancer, Laryngeal Cancer
Conditions
Keywords
Induction chemotherapy, Immunotherapy, Toripalimab, Radiotherapy
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.
Interventions
DRUGToripalimab
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).
Sponsors
Fudan University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival | 2 year | From the rate of enrollment to first progression |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Locoregional recurrence-free survival | 2 year | From the rate of enrollment to first locoregional relapse |
| Distant metastasis-free survival | 2 year | From the rate of enrollment to first distant metastasis |
| Overall response rate of induction chemotherapy | up to 3 month | Overall response rate of induction chemotherapy, evaluated by MR/CT imaging per RECIST 1.1 |
| Laryngeal Preservation Rate | 2 year | The incidence of those with partial/whole preservation of anatomic larynx, without evidence of local recurrence |
| Adverse Effect | up to 2 year | Adverse Effect, evaluated by CTCAE 4.0.03 |
| Overall survival | 2 year | From the rate of enrollment to death |
Countries
China
Contacts
Primary ContactXiayun He, M.D.
Backup ContactYu Wang, M.D.
Outcome results
None listed