Prospective, One-arm, Phase II Clinical Study of Tirelizumab in Combination With Carboplatin and Albumin-binding Paclitaxel for Neoadjuvant Therapy in Patients With Resectable Squamous Cell Carcinoma of the Head and Neck
Overview
- Phase
- Phase 2
- Intervention
- Tirelizumab ,+Carboplatin+albumin-bound paclitaxel
- Conditions
- Head and Neck Squamous Cell Carcinoma
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Major pathologic response
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
In this study, 100 patients with resectable head and neck squamous cell carcinoma (oral squamous cell carcinoma and oropharyngeal squamous cell carcinoma) were enrolled, who were combined with tirelizumab, carboplatin and albumin-binding paclitaxel before and after surgery. Tumor tissues and paracancer tissues of patients were collected to observe the imaging and pathological changes before and after treatment. At the same time, clinical information of patients, such as pathological grade, stage, treatment, prognosis, serology, imaging, etc. were collected to evaluate the safety and feasibility of tirelizumab combined with carboplatin and albumin-binding paclitaxel for neoadjuvant therapy of resectable oral and oropharyngeal squamous cell carcinoma. This is a prospective, one-arm, phase II clinical study.
Purpose Main purpose The efficacy of Tirelizumab combined with carboplatin and albumin-paclitaxel in neoadjuvant therapy for resectable head and neck squamous cell carcinoma was evaluated by calculating the major pathological response (MPR) rates in the experimental group.
The severity of adverse events associated with neoadjuvant therapy will be graded according to NCI CTCAE (version 5.0) during the course of this study and during follow-up, the incidence of adverse events in the experimental and control groups will be compared, and the safety of neoadjuvant therapy with Tirelizumab combined with carboplatin and albumin-paclitaxel in resectable head and neck squamous cell carcinoma will be evaluated.
Secondary Purpose
- One-year event survival rate and event-free survival (EFS) of enrolled patients were evaluated (five years);
- Pathological complete response rate (pCR) of enrolled patients was evaluated (5 years);
- pTR of enrolled patients was evaluated;
- Overall survival (OS) of enrolled patients was evaluated (5 years);
- Radiological response of enrolled patients was assessed;
- The rate of operation delay of enrolled patients was evaluated;
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 years of age ≤65 years of age;
- •Cytological or histological diagnosis of surgically resectable squamous cell carcinoma of the head and neck with the following stages:
- •T3-4a, N0-2, M0;
- •According to the solid tumor efficacy evaluation criteria (RECIST version 1.1), there was at least one radiologically measurable lesion; First-line patients: have not previously received any systemic antitumor therapy for advanced/metastatic disease. Patients who had previously received platinum-containing adjuvant/neoadjuvant chemotherapy, or had received radical chemoradiotherapy for advanced disease, if the interval between disease progression or recurrence and the end of the last chemotherapy drug treatment was at least 6 months, were allowed to be enrolled in this study.
- •ECOG score 0-1;
- •Expected survival time \> 3 months;
- •Adequate organ function, subject shall meet the following laboratory indicators:
- •The absolute value of neutrophil granulocyte (ANC) ≥1.5x109/L in the last 14 days without the use of granulocyte colony stimulating factor;
- •Platelets ≥100×109/L without blood transfusion in the past 14 days;
- •Hemoglobin \> without blood transfusion or use of erythropoietin within the last 14 days; 9g/dL;
Exclusion Criteria
- •Malignant diseases other than head and neck squamous cell carcinoma diagnosed within 5 years prior to initial administration (excluding basal cell carcinoma of the skin after radical treatment, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical excision);
- •Currently participating in an interventional clinical study, or receiving other investigational drugs or using investigational devices within 4 weeks prior to initial dosing;
- •Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulus or synergistic inhibition of T cell receptors (e.g., CTLA-4, OX-40, CD137);
- •Systemic treatment with Chinese patent drugs or immunomodulatory drugs (including thymosin, interferon and interleukin, except for local use to control pleural effusion) with indications of anti-head and neck squamous cell carcinoma within 2 weeks before the first administration;
- •An active autoimmune immune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to initial administration. Alternative therapies (such as thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy;
- •Was receiving systemic glucocorticoid therapy (excluding nasal, inhalation, or other routes of topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to initial administration; Note: Physiological doses of glucocorticoids (≤10 mg/ day of prednisone or equivalent) are permitted;
- •Clinically uncontrollable pleural effusion/abdominal effusion (patients with no need to drain effusion or no significant increase of effusion after 3 days of stopping drainage could be included in the group);
- •Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
- •Those who are known to be allergic to the active ingredients or excipients of the drug in this study, Pabolizumab, carboplatin and albumin-binding paclitaxel;
- •Has not fully recovered from toxicity and/or complications caused by any intervention before starting treatment (i.e., ≤ grade 1 or baseline, excluding weakness or hair loss);
Arms & Interventions
Arm 1
Drug:Tirelizumab , Carboplatin,albumin-bound paclitaxel Patients receive Tirelizumab IV on day 1, albumin-bound paclitaxel IV on day 1 and carboplatin IV on day 1 . Treatment repeats every 21 days for up to 2cycles in the absence of disease progression or unacceptable toxicity. Then surgery.
Intervention: Tirelizumab ,+Carboplatin+albumin-bound paclitaxel
Outcomes
Primary Outcomes
Major pathologic response
Time Frame: 6 weeks
Pathologic response rate to neoadjuvant treatment in resected tumor and lymph nodes. The rate of major pathologic response, defined as \<10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.
Adverse events graded by CTCAE v5.0
Time Frame: 90 days after surgery
Percentage of adverse events that are possibly, probably or definitely related to study treatment per Criteria for Adverse Events version 5 (CTCAE v5.0).
Secondary Outcomes
- Radiographic Response(6 weeks)
- Overall survival（OS）(5 years)
- Event-free survival (EFS)(1 years and 5 years)
- Operation delay rate(2months)
- Pathologic complete response(6 weeks)