NCT05136768尚未招募2 期
Phase II Clinical Study of Sintilimab Combined With Platinum-based Chemotherapy and SBRT in the First-line Treatment of Limited Metastatic Head and Neck Squamous Cell Carcinoma
Jun-Lin Yi, MD1 个研究点 分布在 1 个国家目标入组 50 人开始时间: 2021年12月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Progression-free survival time (PFS)
研究概览
简要总结
To evaluate the safety and efficacy of combination of Sintilimab and SBRT on the basis of platinum-containing chemotherapy as the first-line treatment of limited metastatic head and neck squamous cell carcinoma (LM-HNSCC).
详细描述
For patients with LM-HNSCC, the conventional first-line treatment is EXTREME regimen dominated systemic therapy. In the recent era, immunotherapy has emerged to be the paramount issue for cancer treatment. A series of high-quality clinical studies demonstrated that immunotherapy (such as PD1 inhibitor) with or without chemotherapy (depending on CPS status) offered significant survival benefits to patients with recurrent or metastatic (R/M) HNSCC and the toxicities were well tolerated, whereas the PFS was still dismal. SBRT is associated with initiating release of tumor antigens, promoting DC activation, activating APCs, priming CD8+ CTLs, leading to the potential of abscopal effect. Therefore, we hypothesized that adding SBRT to Sintilimab (a PD1 inhibitor) and platinum-containing chemotherapy as the first-line treatment may improve the PFS for limited metastatic head and neck squamous cell carcinoma (LM-HNSCC).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Sign written informed consent before implementing any trial-related procedures;
- •Male or female, age ≥18 years old;
- •Histologically confirmed head and neck squamous cell carcinoma, which was diagnosed as initial stage IVC/M1(synchronous metastatic disease) according to the 8th edition of UICC/AJCC or previously treated head and neck tumor with newly occurred metachronous metastatic disease ;
- •Pathological diagnosis of metastasis is not mandatory, but the clinical diagnosis needs to receive consent of MDT;
- •The number of metastases is 1-10;
- •PD-L1 expression is positive, CPS≥1;
- •According to the evaluation criteria for the efficacy of solid tumors (RECIST version 1.1), at least one metastatic lesion is radiologically measurable;
- •Newly-diagnosed HNSCC who has not received any treatment previously or HNSCC who has been diagnosed metastases for the first time after treatment;
- •For patients who have received platinum-containing chemotherapy in the past, the interval between the new metastasis and the end of the last chemotherapy administration is at least 6 months;
- •After a comprehensive radiological examination, at least one extracranial metastatic lesion with a maximum diameter of ≤ 5cm (which can be treated with SBRT);
- •ECOG score 0-1 points;
- •Sufficient organ function, subjects need to meet the following laboratory indicators: In the past 14 days without using granulocyte colony stimulating factor, the absolute value of neutrophils (ANC) ≥ 1.5x109/L. In the case of no blood transfusion in the past 14 days, platelets ≥100×109/L. In the past 14 days without blood transfusion or using erythropoietin, hemoglobin>9g/dL；Total bilirubin≤1.5×upper limit of normal (ULN); or total bilirubin>ULN but direct bilirubin≤ULN；Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are within ≤2.5×ULN;Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥60 ml/min; Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN;Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is outside the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group;The myocardial enzyme spectrum is within the normal range (if the investigator comprehensively judges that the simple laboratory abnormality is not of clinical significance, it is also allowed to be included);
- •Expected survival> 1 year;
- •At least one lesion is RECIST 1.1 assessable lesion;
- •No previous PD1 or PD-L1 inhibitor treatment history;
- •Without comorbidities that needs treatment of immunodepressant;
- •Male subjects and women of childbearing age must have contraception within 24 weeks from the start of the study to the last time of using the drug.
排除标准
- •The primary site is squamous cell carcinoma of the nasopharynx or skin cancer.
- •The number of metastases>10;
- •Patients who have been diagnosed with other malignant tumors within 5 years before the first administration and have not been cured (excluding radically cured skin basal cell carcinoma, skin squamous epithelial carcinoma, and/or radically resected carcinoma in situ);
- •Currently participating in interventional clinical research treatment, or received other research drugs or used research devices within 4 weeks before the first administration;
- •Have received the following therapies in the past: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or for another stimulating or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) drug;
- •Received systemic treatment with anti-tumor indications Chinese patent medicines or immunomodulatory drugs (including thymosin, interferon, interleukin, except for local use to control pleural fluid) within 2 weeks before the first administration;
- •An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
- •Administration of systemic steroid (not include nasal spray, inhalation or other local approach) within 7 days before the first administration of Sintilimab or any other ways of immunosuppression;
- •Receiving Xenografts or allogeneic hematopoietic stem cell transplantation in the past;
- •Allergic to component of research drugs or adjacent;
- •HIV infection;
- •Untreated active hepatitis B (HBsAg positive and HBV-DNA copy number larger than upper limit of threshold);
- •Untreated active hepatitis C (HCV antibody positive and HCV-RNA larger than upper limit of threshold);
- •Inoculation with live vaccine within 30 days before the first administration of Sintilimab;
- •Women patients in the pregnancy or lactation period;
- •With severe or uncontrollable comorbidity.
研究组 & 干预措施
Single arm
Experimental
Sintilimab combined with platinum-based chemotherapy and SBRT
干预措施: Sintilimab (Drug)
Single arm
Experimental
Sintilimab combined with platinum-based chemotherapy and SBRT
干预措施: SBRT (Radiation)
Single arm
Experimental
Sintilimab combined with platinum-based chemotherapy and SBRT
干预措施: Platinum based chemotherapy (Drug)
结局指标
主要结局
Progression-free survival time (PFS)
时间窗: Up to 2 years
PFS is defined as the duration from the starting date of per-protocol treatment to first progression of disease, death or closure of study.
次要结局
- Time to progression of initial lesions (TPIL)(Up to 2 years)
- Time to progression of non-irradiated lesions (TPNRL)(Up to 2 years)
- Objective response rate (ORR)(Up to 1 years)
- Overall survival time (OS)(Up to 2 years)
- Duration of disease response (DOR)(Up to 2 years)
- Disease control rate (DCR)(Up to 1 years)
- Time to progression of new lesions (TPNL)(Up to 2 years)
- Adverse events(Up to 2 years)
研究者
Jun-Lin Yi, MD
Vice director of Dept. Radiotherapy
Chinese Academy of Medical Sciences
研究点 (1)
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