Clinical trial NCT06366945: Tirelizumab in Combination With Carboplatin and Polymeric Micellar Paclitaxel for Neoadjuvant Therapy in cN+ HNSCC
Official title: Prospective, Single-arm, Phase II Clinical Study of Tirellizumab Combined With Carboplatin and Paclitaxel Polymer Micelles Neoadjuvant Therapy for cN+ Head and Neck Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Head and Neck Squamous Cell Carcinoma
Head and Neck Cancer
HNSCC
Head Cancer Neck
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 85
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
Primary purpose: TREATMENT

Brief summary: To explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for resectable HNSCC patients with clinical positive lymph node metastasis

Detailed description: The 5-year overall survival rate of patients with clinical N-positive head and neck squamous cell carcinoma (HNSCC) is less than 50%, and the clinical outcomes of these patients still need improvement.

Immunotherapy, such as PD-1/PD-L1 inhibitors, has shown excellent efficiency in treating malignant tumors. Anti PD-1 therapy has been approved as a first-line treatment for recurrent/metastatic HNSCC. The results of several phase II clinical trials have shown that neoadjuvant immunotherapy for locally advanced resectable HNSCC has been proven to be safe and feasible. However, immunotherapy has a lower MPR rate for locally advanced HNSCC patients with lymph node metastasis.

Paclitaxel has been used as a first-line induction therapy for locally advanced HNSCC and is an important drug in mediating immunogenic death, enhancing the efficacy of immunotherapy. Previous studies on lung cancer have confirmed that nano-paclitaxel has better induction efficacy than solvent paclitaxel and reduces the rate of distant metastasis.

In summary, the investigators designed this study to explore the efficiency and safety of Tislelizumab combinated with carboplatin and polymeric micellar paclitaxel as a new neoadjuvant treatment regimen for patients with clinical N positive resectable HNSCC, aiming to provide a new treatment option for those patients.

Eligibility criteria: Inclusion Criteria:

Males and females ECOG Performance Status 0 or 1. Confirmed pathologic and/or cytologic diagnosis of squamous cell carcinoma of head and neck，T2-4N1-3M0（III-IV）（AJCC 8.0） Histological diagnosis of squamous cell carcinoma of the lip, oral cavity, oropharynx, hypopharynx, larynx.

With measurable target lesions by CT or MRI. Adequate bone marrow function. Adequate renal and liver function. Pregnancy test (for patients of childbearing potential) negative at screening. Signed Written Informed Consent.

Exclusion Criteria:

Patients who pathologically confirmed non-squamous cell carcinoma Patients who has recurrence or distant metastasis Local lesions have been surgically removed Patients who have received systemic anti-cancer therapy, including hormone therapy Patients who have received treatment targeting PD-1 or PD-L1 Patients with active autoimmune disease or a history of autoimmune disease but may relapse(Patients with the following diseases are not excluded and can be further filtered) Controlled type 1 diabetes Hypothyroidism(If it can be controlled with hormone replacement therapy) Controlled celiac disease Skin diseases that do not require systemic treatment such as Vitiligo, Psoriasis and Hair loss.

Any other disease that is not expected to recur without external triggers Any active malignant tumors within 2 years before treatment, except for the specific cancers being studied in this trial and locally recurring cancers that have been cured (such as resected basal cell or squamous cell skin cancer, superficial bladder cancer, cervical in situ Cancer or breast cancer) Any disease requiring systemic treatment with corticosteroids (referring to treatment with a dose higher than 10 mg/day of prednisone or equivalent doses of similar drugs) or other immunosuppressive treatments within 14 days before treatment.

However, patients who have currently or previously used any of the following steroid regimens can be selected:

Adrenaline replacement steroids(Prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic, intra-articular, intranasal and inhaled corticosteroids which is Systemic absorbed Minimally Prophylactically short-term (≤7 days) use of corticosteroids (for example, allergy to contrast agents) or for the treatment of non-autoimmune conditions (for example, delayed hypersensitivity reactions caused by contact allergens) Uncontrolled diabetes within 14 days before treatment or laboratory abnormalities with potassium, sodium and corrected calcium levels\> 1 after standard drug treatment or hypoalbuminemia grade ≥ 3 History of the following diseases: interstitial lung disease, non-infectious pneumonia or uncontrollable diseases, including pulmonary fibrosis, acute lung disease, etc.

Severe chronic or active infection (including tuberculosis infection, etc.) that required systemic antibiotics, antibacterial or antiviral treatment occurred within 14 days before the first administration of the study drug The patient is known to have been infected with HIV Untreated patients with chronic hepatitis B or HBV carriers with chronic hepatitis B virus (HBV) DNA ≥ 500 IU/mL or active hepatitis C virus carriers (HCV) should be excluded.

Patients can be selected who is Inactive hepatitis B surface antigen (HBsAg) carriers, treated and stable hepatitis B patients (HBV DNA \<500 IU/mL) and cured hepatitis C patients.

Any surgery requiring general anesthesia has been performed within 28 days before treatment Have had allogeneic stem cell transplantation or organ transplantation

Have any of the following cardiovascular risk factors:

Cardiogenic chest pain within 28 days before treatment(moderate pain that restricts instrumental activities of daily living) Symptomatic pulmonary embolism within 28 days before treatment Acute myocardial infarction within 6 months before treatment Any history of heart failure that has reached Grade III or IV as defined by the New York Heart Association within 6 months before treatment Grade 2 ventricular arrhythmia within 6 months before the first administration of the study drug Have a history of cerebrovascular accident within 6 months before the first administration of the study drug Have a history of severe hypersensitivity to other monoclonal antibodies Patients with treatment toxicity (caused by previous anti-cancer treatments) have not returned to baseline or stabilized, unless it is an AE that is not considered a possible safety risk (such as hair loss, neuropathy, or specific laboratory abnormalities) History of allergic reactions to cisplatin or other platinum-containing compounds Peripheral nerve disease ≥ Grade 2 defined by NCI CTCAE v5.0 standard Have gotten a live vaccine within 4 weeks before treatment(Seasonal flu vaccines are usually inactivated vaccines and are allowed to be used; The vaccine used in the nasal cavity is a live vaccine and is not allowed to be used) Abuse or dependence on alcohol or drugs and Basic medical conditions (including laboratory abnormalities) that are not conducive to the administration of the study drug , affect the interpretation of drug toxicity or AEs, lead to insufficient compliance with the study execution and possible damage The patient participates in another therapeutic clinical study at the same time

Primary outcomes:
measure: Major pathological response (MPR) rate of metastatic lymph nodes
timeFrame: 10days after surgery
Secondary outcomes:
measure: Major pathological response (MPR) rate of primary tumor
timeFrame: 10days after surgery
measure: Event-free survival (EFS)
timeFrame: 1 years and 3 years
measure: Overall survival（OS）
timeFrame: 1 years and 3 years
measure: Incidence of treatment-related adverse events
timeFrame: from the first day of treatment to 30 days after surgery；if adjuvant immotherapy is omitted, time frame is from the first day of treatment to 30 days after last administration
measure: EORTC QLQ-C30
timeFrame: from 1 week before treatment to 30 days after surgery
measure: pathological downstaging rate
timeFrame: 10days after surgery
measure: Distant metastasis-free survival(DMFS) rate
timeFrame: 1 year and 3 year
measure: logical regional-free survival(LRFS) rate
timeFrame: 1 year and 3 year
Other outcomes:
measure: Correlation between ctDNA dynamic detection and 1-year and 2-year EFS and OS rate after Neoadjuvant immunochemotherapy
timeFrame: Six months after consolidation treatment
Locations:
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: jinsong li, doctor
role: STUDY_DIRECTOR
References: