A Phase II, Single-center, Prospective, Randomized, Controlled Study of Induction Chemotherapy With AP Regimen Plus Anti-PD-1 Antibody JS001 (Toripalimab) for Resectable Locally Advanced Squamous Cell Carcinoma of Head and Neck
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 122
- 试验地点
- 1
- 主要终点
- PCR
研究概览
简要总结
The objective of research is to evaluate the efficacy and safety of Toripalimab combined with AP regimen in the treatment of resectable locally advanced head and neck squamous cell carcinoma.122 patients were randomly divided into two groups: the test group (Toripalimab combined with AP ) and the control group (AP ); The patients in both groups were treated with three cycles of induction therapy. After the induction therapy, the patients were evaluated and followed up with surgery.
详细描述
The case report form shall be filled by the investigator, and each selected case must complete the case report form. The completed case report form is used for data entry and management.
All original data were retained by the research department.Full analysis set: according to the principle of intention to analyze (ITT), all cases who received drug treatment and took drugs at least once were analyzed for efficacy. For the case data that cannot observe the whole treatment process, the last observation data shall be carried forward to the final results of the study (LOCF).
Per-protocol set: all cases that comply with the study protocol, have good compliance, have not taken prohibited drugs during the study period, and have completed the contents specified in the case report form. No imputation was performed for missing data. Fas and PPS were analyzed statistically for the efficacy of the drug.
Safety analysis set: all enrolled patients who have used the study drug at least once and have safety records after drug use belong to the safety analysis set. This data set was used for safety analysis.
All statistical analysis will be calculated by SPSS statistical analysis software. All statistical tests are conducted by two-sided test. If the p value is less than or equal to 0.05, the difference tested will be considered statistically significant. The confidence interval is 95%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years, male or female;
- •Patients with squamous cell carcinoma of head and neck confirmed by histopathology or cytopathology;
- •Surgical resection available, clinical stage III or IV without distant metastasis (AJCC 8th)
- •Patients who have not received any prior anti-tumor therapy such as chemotherapy, radiotherapy, immunotherapy or biological therapy;
- •At least one measurable lesion according to RECIST 1.1 (Appendix 1)
- •ECOG performance status 0-1 (Appendix 2);
- •Expected survival ≥3 months;
- •Function of vital organs meets the following requirements (no blood component, cell growth factor, white blood cell-raising drug, platelet-raising drug, and blood correction drug is allowed within 14 days prior to the first dose of study drug); A.WBC≥3.0x109 /L, ANC≥2.0x109/L B.HB≥90g/L C.Platelets ≥ 100 × 10 9/L D.Serum albumin ≥2.8 g/dL E.Bilirubin total ≤ 1.5 x ULN, ALT ≤ 3.0 x ULN F.Serum creatinine ≤ 1.5xULN or Creatinine clearance > 60 mL/min G.Activated partial thromboplastin time (APTT) and International normalized ratio (INR) ≤ 1.5 x ULN (screening is allowed for stable doses of Anticoagulant therapy such as low molecular weight heparin or warfarin with INR within the expected therapeutic range of anticoagulants)
- •No contraindication to chemotherapy or immunotherapy;
- •No history of immune-related disease;
- •No uncontrolled pneumonia or lung infection;
- •Women of childbearing age must agree to use effective contraceptive measures during the trial; serum or urine pregnancy test must be negative within 72 hours before the first dose of study treatment;
- •Good compliance: able to receive the treatment and follow-up, and voluntary to comply with the regulations of the study;
- •Patients voluntarily sign the informed consent form.
排除标准
- •Patients with distant metastasis;
- •Uncontrolled severe medical diseases, e.g., severe heart disorder (New York Heart Association class II or higher; Appendix 3), cerebrovascular angiopathy, uncontrolled diabetes mellitus, uncontrolled hypertension, uncontrolled infection, active peptic ulcer, etc., combined with these medical diseases;
- •Previous history of allergy to any component of monoclonal antibody or allergic constitution;
- •Uncontrolled cardiac symptoms or diseases, such as NYHA class II or higher Cardiac failure or left ventricular Ejection fraction (LVEF) <50% as indicated by cardiac echocardiography, Angina unstable, Myocardial infarction within 1 year, patients with clinically significant supraventricular or Ventricular arrhythmia requiring clinical intervention (including QTc interval ≥ 470 ms);
- •Serious infection (NCI CTCAE > Grade 2) occurred within 4 weeks before the first dose of the study drug, such as severe pneumonia, bacteraemia, and infectious complications requiring hospitalisation; Baseline chest imaging suggests active pneumonitis, symptoms and signs of infection within 2 weeks before the first dose of the study drug, or oral or intravenous antibiotic therapy is required for treatment (excluding the use of antibiotics for prophylaxis);
- •Unexplained fever >38.5℃ occurred during the screening period and prior to the first dose (tumor fever judged by the investigator could be enrolled);
- •Active autoimmune disease or history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); but not including autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormones; type I diabetes mellitus treated with stable doses of insulin; vitiligo or healed childhood asthma/allergy that does not require any intervention after adulthood;
- •History of immunodeficiency, including HIV-positive test, or other acquired, immunodeficiency congenital diseases, or history of organ transplant and allogeneic bone marrow transplant;
- •Patients with untreated Chronic hepatitis B or chronic HBV DNA exceeding 500 IU/ml or patients with active Hepatitis C virus (HCV) should be excluded; patients with inactive Hepatitis B surface antigen who have been treated and are stable (HBV DNA<500IU/ml) and patients with cured Hepatitis C can be enrolled;
- •History of interstitial lung disease (excluding Radiation pneumonitis not induced by previous use of hormone therapy) and Noninfectious pneumonitis;
- •Patients with active pulmonary tuberculosis infection identified through medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year ago but not receiving regular treatment;
- •Patients who have received any of the following treatments:
- •A.Use of any investigational product within 4 weeks prior to the first dose of study drug B.Receiving the last dose of antitumor therapy (including chemotherapy, radiotherapy, targeted therapy, etc.) within ≤4 weeks prior to the first dose of the study drug C.Patients who require corticosteroids (daily > 10 mg prednisone equivalent dose) or other immunosuppressants for systemic treatment within 2 weeks prior to the first dose of investigational product, except for the use of corticosteroids for treatment of inflammation localised and prevention of allergic reactions and nausea and vomiting, were excluded. In the absence of active autoimmune disorder, inhaled or topical use of steroids and adrenal corticosteroid replacement with a therapeutic dose > 10 mg/day of prednisone were allowed.
- •D.Having received an antitumor vaccine or any live vaccine within 4 weeks prior to the first dose of the investigational drug E.Major surgery or serious trauma within 4 weeks prior to the first dose of study drug F.Enrollment in another clinical study
- •Dementia, mental status changes, or any psychiatric disorder that, in the Investigator's judgment, would interfere with the understanding, giving, or maintenance of informed consent or completion of the questionnaires;
- •Patients with ≥ grade 2 peripheral neuropathy according to NCI CTCAE version 5.0;
- •History of allergy or Hypersensitivity to any treatment component;
- •History of primary Neoplasm malignant other than squamous cell carcinoma of head and neck within the past 5 years, except for adequately treated basal cell or squamous epithelial skin cancer, localized prostate cancer after radical prostatectomy, and ductal carcinoma in situ after radical operation;
- •Those requiring concomitant treatment with other anti-tumor drugs;
- •Unsuitable for inclusion as determined by the investigator;
- •Pregnant or breast-feeding women
研究组 & 干预措施
Toripalimab combined with AP
Nab-Paclitaxel : 260 mg/m2, intravenous infusion, d1, 3-week cycle, 3 cycles; Cisplatin: 75 mg/m2, intravenous infusion, d1, once every 3 weeks, for a total of 3 cycles; Toripalimab : 240 mg, intravenous infusion, d1, once every 3 weeks, for a total of 3 cycles.
干预措施: AP combined with or without Toripalimab (Drug)
AP (Nab-Paclitaxel + Cisplatin)
Nab-Paclitaxel: 260 mg/m2, intravenous infusion, d1, 3-week cycle, 3 cycles in total; Cisplatin: 75 mg/m2, intravenous infusion, d1, once every 3 weeks, for a total of 3 cycles;
干预措施: AP combined with or without Toripalimab (Drug)
结局指标
主要结局
PCR
时间窗: 9 weeks
Pathological complete response rate
PCR
时间窗: 12 weeks
Pathological complete response
次要结局
- MPR(9 weeks)
- MPR(12 weeks)