Postponing or Omitting Re-irradiation After Tislelizumab Plus Chemotherapy in Unresectable Recurrent Loco-regionally Advanced Nasopharyngeal Carcinoma
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Progress-free survival (PFS)
研究概览
简要总结
This is an open-label, multi-center, phase II trial to evaluate the safety and efficacy of postponing or omitting re-irradiation after systemic therapy with tislelizumab and chemotherapy in patients with unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. Patients who did not respond to or progressed on another ICI are allowed to receive tislelizumab rechallenge as a subgroup.
详细描述
High dose reirradiation is usually recommended for unresectable recurrent loco-regionally advanced nasopharyngeal carcinoma. However, it potentially adds to the RT-related severe toxicities and deaths. This trial aims to investigate the feasibility of postponing or even omitting re-irradiation based on effective first-line systemic therapy with tislelizumab and chemotherapy. For patients that progressed after exposure to another PD-1 antibody,tislelizumab rechallenge is accepted as a second subgroup.In this trial, all patients will receive chemotherapy (on doctors' recommendation) and PD-1 antibody (tislelizumab 200mg every three weeks). Patients with no response to the systemic therapy will receive salvage low dose re-irradiation delivered by SBRT, while those who showed complete or partial response will continue maintenance therapy until progression, death or intolerable toxicity, and reirradiation will be postponed or omitted.
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
- 15 Years 至 90 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed as local recurrence ± regional recurrence after ≥1 year of radical treatment;
- •Not suitable for surgery;
- •Clinical stage rT3-4N0-2 (rII-IVa, AJCC/UICC 8th);or residual disease afer surgery.
- •ECOG score 0-1;
- •No prior treatment to rNPC, such as radiotherapy, chemotherapy, immunotherapy or biotherapy;
- •No contraindications to immunotherapy or chemoradiotherapy;
- •Adequate marrow function: WBC count ≥ 3×10E9/L, NE count ≥ 1.5×10E9/L, HGB ≥ 90g/L, PLT count ≥ 100×10E9/L;
- •Adequate liver function: ALT/AST ≤ 2.5×ULN, TBIL ≤ 2.0×ULN;
- •Adequate renal function: BUN/CRE ≤ 1.5×ULN or endogenous creatinine clearance ≥ 60ml/min (Cockcroft-Gault formula);
- •Take effective contraceptions during and two months after treatment;
- •Patients must be informed of the investigational nature of this study and give written informed consent.
排除标准
- •Have local necrosis in recurrent lesions, estimated with bleeding risk;
- •Unexplained fever > 38.5 ℃, except for tumor fever;
- •Treated with ≥ 5 days antibiotics one month before enrollment;
- •Have active autoimmune disease (e.g., uveitis, enteritis, hepatitis, hypophysitis, nephritis, vasculitis, hyperthyroidism, and asthma requiring bronchodilator therapy);
- •Have a known history of human immunodeficiency virus (HIV), active Hepatitis B (HBV-DNA ≥10E3copiers/ml) or hepatitis C virus (HCV) antibody positive;
- •Have ≥G3 late toxicities, except for skin, subcutaneous tissue or mucosa;
- •Have New York Heart Association (NYHA) class 3 or 4, unstable angina, myocardial -infarction within 1 year, or clinically meaningful arrhythmia that requires treatment;
- •Have known allergy to large molecule protein products or any compound of study therapy;
- •Pregnant or breastfeeding;
- •Prior malignancy except adequately treated non-melanoma skin cancer, in situ cervical cancer, and papillary thyroid carcinoma;
- •Any other condition, including mental illness or domestic/social factors, deemed by the investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interferes with the interpretation of the results.
研究组 & 干预措施
Experimental
Main group: Patients will be given first line tislelizumab plus investigator's choice chemotherapy, with re-irradiation postponed or omitted.
Subgroup: For patients that progressed after exposure to another PD-1 antibody, tislelizumab rechallenge combined with either low dose SBRT or low dose gemcitabine and metronomic capecitabine is accepted as a second subgroup.
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Progress-free survival (PFS)
时间窗: 2 year
Defined from date of enrollment to date of first documentation of progression or death due to any cause.
Objective response rate (ORR)
时间窗: 3 months
Defined as either a confirmed CR or a PR, as determined by the investigator using RECIST v1.1Response Evaluation Criteria in Solid Tumors (RECIST) .
次要结局
- Adverse events (AEs)(2 year)
- Overall survival (OS)(2 year)
- Quality of life (QoL)(1 year)
研究者
Xiaoshen Wang
Director of Department of Radiation Oncology
Fudan University