Decitabine Plus Penpulimab as Second-line Therapy for Advanced ESCC Treated With PD-1 Blockade
2022年2月23日 更新者:Feng Wang、The First Affiliated Hospital of Zhengzhou University
An Single-arm Open-label Phase II Study of Decitabine Plus Penpulimab as Second-line Therapy for Advanced Esophageal Squamous Cell Carcinoma Treated With PD-1 Blockade
The purpose of this study is to observe and evaluate the efficacy and safety of Decitabine plus Penpulimab as second-line therapy for advanced esophageal squamous cell carcinoma treated with PD-1 blockade
研究概览
详细说明
Although immune checkpoint inhibitors (ICIs) have been tested in esophageal squamous cell carcinoma(ESCC) with demonstrated clinical efficacy,a significant number of patients have an initial response will develop a secondary resistance and relapse.
recent studies on the role of epigenetics in immune evasion have exposed a key role for epigenetic modulators in augmenting the tumour microenvironment and restoring immune recognition and immunogenicity.
These discoveries have established a highly promising basis for studies using combined epigenetic and immunotherapeutic agents as anti-cancer therapies.
Decitabine is a novel orally active benzamide-type histone deacetylase inhibitor that has shown in vitro activities against a wide array of neoplasms.
Hence, the study of decitabine plus penpulimab(AK-105) as second-line therapy for advanced ESCC treated with PD-1 blockade was performed.
研究类型
介入性
注册 (预期的)
85
阶段
- 阶段2
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments.
- Age ≥ 18 years on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).
- Histologically confirmed diagnosis of ESCC.
- Have PD after first-line of PD-1 blockade treatment for unresectable, locally advanced, recurrent or metastatic ESCC.
- Measurable disease per RECIST v1.1 assessed by the local investigator
- ECOG PS 0 or 1
- Newly obtained (preferred) or archival tissue sample available
- Negative urine or serum pregnancy test within 72 h before randomization (females)
- Willing to use an adequate method of contraception throughout the study and for 120 days after the last dose of study medication and up to 180 days after the last dose of cisplatin
- Adequate haematologic function, defined as ANC ≥ 1500/μl, platelet count ≥ 100,000/μl and haemoglobin ≥ 9.0 g/dl or ≥5.6 mmol/l
- Adequate renal function, defined as creatinine ≤ 1.5 × ULN or measured or calculated creatinine clearance ≥ 60 mL/min for those with creatinine levels 1.5 × ULN
- Adequate hepatic function, defined as total bilirubin ≤1.5 × ULN or direct bilirubin ≤ ULN for those with total bilirubin levels 1.5 × ULN, and ALT/AST levels ≤ 2.5 × ULN
- Adequate coagulation function, defined as INR ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case PT or aPTT should be within the therapeutic range
- Written informed consent
Exclusion Criteria:
- Patients with evidence of fistula (either esophageal/bronchial or esophageal/aorta).
- Evidence of complete esophageal obstruction not amenable to treatment.
- Active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- Active autoimmune diseases or history of autoimmune diseases that may relapse
- Any active malignancy ≤ 2 years before randomization except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast).
- Uncontrolled diabetes or > Grade 1 laboratory test abnormalities in potassium, sodium, or corrected calcium despite standard medical management or ≥ Grade 3 hypoalbuminemia ≤ 14 days before initial treatment .
- Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage (recurrence within 2 weeks after intervention).
- History of interstitial lung disease, noninfectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc.
- Infection (including tuberculosis infection, etc) that requires systemic antibacterial, antifungal or antiviral therapy within 14 days beforeinitial treatment
- A history of severe hypersensitivity reactions to chidamide and monoclonal antibodies.
- Patients with toxicities (as a result of prior anticancer therapy) that have not recovered to ≤Grade 2 or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities).
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
实验性的:Decitabine plus Penpulimab
Pts received decitabine 10mg/d IV daily x5 every 3 weeks and penpulimab(AK-105) 200 mg intravenously every 3 weeks until disease progression, unacceptable adverse events (AEs) or withdrawal of consent.
|
Pts received decitabine 10mg/d IV daily x5 every 3 weeks and penpulimab(AK-105) 200 mg intravenously every 3 weeks until disease progression, unacceptable adverse events (AEs) or withdrawal of consent.
|
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
OS
大体时间:up to 24 months
|
From date of initial treatment until the date of death from any cause
|
up to 24 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
ORR
大体时间:up to 24 months
|
Defined as the proportion of patients with a documented complete response, partial response(CR+PR)
|
up to 24 months
|
PFS
大体时间:Up to 24 months
|
From date of initial treatment until the date of first documented progression or date of death from any cause
|
Up to 24 months
|
DOR
大体时间:up to 24 months
|
Refers to the time when the tumor is first evaluated as CR or PR until the first assessment is PD (Progressive Disease) or any cause of death.
|
up to 24 months
|
DCR
大体时间:up to 24 months
|
Defined as the proportion of patients with a documented complete response, partial response and stable response(CR+PR+SD)
|
up to 24 months
|
Adverse Events (Safety)
大体时间:up to 24 months
|
Adverse Events
|
up to 24 months
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Tumor mutation burden (TMB)
大体时间:up to 24 months
|
Total number of non-synonymous mutations in each coding region of the tumor genome
|
up to 24 months
|
PD-L1 CPS
大体时间:up to 24 months
|
Number of PD-L1 staining cells (tumor cells)/Total tumor cellsk*100%
|
up to 24 months
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (预期的)
2022年12月1日
初级完成 (预期的)
2023年12月31日
研究完成 (预期的)
2024年12月31日
研究注册日期
首次提交
2022年2月7日
首先提交符合 QC 标准的
2022年2月23日
首次发布 (实际的)
2022年3月4日
研究记录更新
最后更新发布 (实际的)
2022年3月4日
上次提交的符合 QC 标准的更新
2022年2月23日
最后验证
2022年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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