Clinical trial NCT05420597: Induction Chemotherapy and Toripalimab Followed by Radiotherapy in Unresectable Laryngeal/Hypopharyngeal Carcinoma
Official title: Induction Chemotherapy and Toripalimab Followed by Radiotherapy in Unresectable Laryngeal/Hypopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Laryngeal Cancer
Hypopharyngeal Cancer
Keywords: Induction chemotherapy
Immunotherapy
Toripalimab
Radiotherapy
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2022-06-15
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 2 year
Secondary outcomes:
measure: Overall response rate of induction chemotherapy
timeFrame: up to 3 month
measure: Locoregional recurrence-free survival
timeFrame: 2 year
measure: Distant metastasis-free survival
timeFrame: 2 year
measure: Overall survival
timeFrame: 2 year
measure: Laryngeal Preservation Rate
timeFrame: 2 year
measure: Adverse Effect
timeFrame: up to 2 year
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xiayun He, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fudan University
name: Yu Wang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: