Pembrolizumab After SBRT Versus Pembrolizumab Alone in Advanced NSCLC (PEMBRO-RT)
Randomized Phase II, 2-arm Study of Pembrolizumab After High Dose Radiation (SBRT) Versus Pembrolizumab Alone in Patients With Advanced Non-small Cell Lung Cancer
研究概览
详细说明
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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Noord-Holland
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Amsterdam、Noord-Holland、荷兰、1066 CX
- Antoni van Leeuwenhoek (NKI-AVL)
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial.
- Be ≥ 18 years of age on day of signing informed consent.
- Have measurable disease based on RECIST 1.1.
- Must provide newly obtained tissue from a core or excisional biopsy of a tumor lesion and are willing to have a second biopsy performed form any non-irradiated lesion after the radiation and immune-modulating treatment.
- Have a performance status of 0 or 1 on the ECOG Performance Scale.
- Stage IV NSCLC; treated with at least 1 regimen of chemotherapy.
- Have at least 2 separate (metastatic) lesions of which one is amenable for irradiation with a size of < 5 cm.
Demonstrate adequate organ function:
Absolute neutrophil count (ANC) ≥1,500 /mcL; Platelets ≥100,000 / mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L; Serum creatinine ≤1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥50 mL/min for subject with creatinine levels > 1.5 X institutional ULN; Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases; International Normalized Ratio (INR) or Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
All screening labs should be performed within 10 days of treatment initiation.
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Exclusion Criteria:
- Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy or targeted small molecule therapy within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
- Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
- Note: If subjects received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- Have had previous radical radiation to any tumor site within 6 months prior to study Day 1.
- Have known but untreated driver mutations of the EGFR gene or ALK translocation.
- Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least six weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment.
9. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjögren's syndrome will not be excluded from the study.
10. Has evidence of symptomatic interstitial lung disease or an active, non-infectious pneumonitis.
11. Has an active infection requiring systemic therapy. 12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
18. Has received a live vaccine within 30 days prior to the first dose of trial treatment.
19. Has had major surgery or major blood transfusions (>3 packed cells) in the past 3 months.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:SBRT + Pembrolizumab
Stereotactic Body Radiation Therapy (SBRT) followed by pembrolizumab treatment within 7 days of completion.
SBRT: 3 x 8 Gy, given 1-2 weeks prior to start of pembrolizumab.
Dose of pembrolizumab is 200 mg, every 3 weeks.
Patients can continue the pembrolizumab treatment for maximal 2 years.
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其他名称:
其他名称:
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有源比较器:Pembrolizumab alone
Dose of pembrolizumab is 200 mg, every 3 weeks.Patients can continue the pembrolizumab treatment for maximal 2 years.
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其他名称:
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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 |
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Overall Response Rate
大体时间:at 12 weeks
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Patients having a partial response or complete response are considered successes, while all other situations are considered failures.
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at 12 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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毒性;毒性发生率,根据国家癌症研究所通用毒性标准 (NCI-CTC) 4.0 版分级
大体时间:治疗结束后最多 30 天
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将在至少接受过一次帕博利珠单抗给药的患者中分析毒性。
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治疗结束后最多 30 天
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The percentage of patients having a complete response, partial response or stable disease at 12 weeks
大体时间:at 12 weeks
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at 12 weeks
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Time from randomization to disease progression or death
大体时间:Until progression, median 5 months
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Until progression, median 5 months
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Time from randomization to death (of any cause).
大体时间:every 12 weeks, median 5 months
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every 12 weeks, median 5 months
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合作者和调查者
调查人员
- 首席研究员:Paul Baas, MD, PhD、Antoni van Leeuwenhoek
- 首席研究员:Willemijn Theelen, MD、Antoni van Leeuwenhoek
出版物和有用的链接
一般刊物
- Theelen WSME, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts JGJV, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021 May;9(5):467-475. doi: 10.1016/S2213-2600(20)30391-X. Epub 2020 Oct 20. Erratum In: Lancet Respir Med. 2021 Mar;9(3):e29.
- Theelen WSME, Peulen HMU, Lalezari F, van der Noort V, de Vries JF, Aerts JGJV, Dumoulin DW, Bahce I, Niemeijer AN, de Langen AJ, Monkhorst K, Baas P. Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non-Small Cell Lung Cancer: Results of the PEMBRO-RT Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Sep 1;5(9):1276-1282. doi: 10.1001/jamaoncol.2019.1478.
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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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