Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel
Phase II Trial of Sequential Consolidation With Pembrolizumab Followed by Nab-paclitaxel After Standard First-Line Induction Chemotherapy in Advanced NSCLC
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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North Carolina
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Chapel Hill、North Carolina、美国、27599
- UNC Lineberger Comprehsive Cancer Center
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Raleigh、North Carolina、美国、27607
- Rex Cancer Center
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Raleigh、North Carolina、美国、27614
- Rex Cancer Center of Wakefield
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Texas
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Dallas、Texas、美国、75390
- UT Southwestern Medical Center
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Virginia
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Fairfax、Virginia、美国、22031
- Inova Schar Cancer Institute
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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 for this trial
- Be greater than or equal to 18 years of age on day of signing consent
- Eastern Cooperative Oncology Group Performance Status less than or equal to 1
- Histologically or cytologically confirmed confirmed stage IV (metastatic) non small cell lung cancer as defined by American Joint Committee on Cancer (AJCC). Recurrent but not metastatic disease is allowed if deemed incurable.
- Has completed or scheduled to begin 4-6 cycles of platinum based induction chemotherapy that does not include a taxane
- Induction may contain, but is not require to contain bevacizumab or cetuximab.
- Induction with a platinum doublet plus another biologic agent will be allowed following review by the University of North Carolina principal investigator that thee is no additional risk to the subject
NOTE: Evaluable disease is not required for study entry (patients with complete response or response sufficient to preclude measurable lesions are not excluded; such patients will be evaluated for progression free survival and overall survival, but not response)
- Demonstrate adequate organ function (defined in protocol). All screening labs should be performed within 14 days of treatment initiation.
- Recovered from all reversible toxicities related to their previous treatment (other than alopecia) less than or equal to grade 1 or baseline; exceptions to this criteria may be allowed at the discretion of the overall principal investigator for toxicities that are not expected to be exacerbated by pembrolizumab or nab paclitaxel
- Patients with brain metastases may participate if they have undergone appropriate treatment for the lesion)s), are at least two weeks post treatment without evidence for post-treatment progression, have no significant neurologic symptoms, and no longer require steroids for the reason of brain metastases
- 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. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year. The two birth control methods can be two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. Subjects should start using birth control from study Visit 1 throughout the study period up to 120 days after the last dose of study therapy.
- 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:
- Patients with epidermal growth factor receptor (EGFR) mutations expected to be sensitive to epidermal growth factor receptor (EGFR) inhibitors and patients with Echinoderm Microtubule-Associated Protein like 4 anaplastic lymphoma kinase (EML4/ALK) translocations are excluded, unless all available FDA approved targeted therapy options have been utilized. NOTE: In contrast to the above a patient with an EGFR mutation who has been treated with a first-generation and third generation TKIs and then with four cycles of carboplatin plus pemetrexed would be eligible
- 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 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 prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1. Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
- Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered from adverse events due to agents administered more than 4 weeks earlier. Exceptions to these criteria may be allowed at the discretion overall principal for toxicities that are not expected to be exacerbated by pembrolizumab or nab-paclitaxel
- 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
- 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 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 Sjorgen's syndrome will not be excluded from the study
- Has evidence of interstitial lung disease or active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- 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
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Has inadequate home environment or social support to safely complete the trial procedures
- 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
- Has received prior therapy with an anti-programmed cell death-1 (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
- Known hypersensitivity to protein bound paclitaxel
- Has received prior therapy with any taxane chemotherapy
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Has known active Hepatitis B or Hepatitis C
- Has received a live vaccine within 30 days prior to the first dose of trial treatment
- Has a history of non-infectious pneumonitis that required steroids or evidence of interstitial lung disease or current active, non-infectious pneumonitis
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:阶乘赋值
- 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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有源比较器:Arm A: Sequential Consolidation
Completion of four cycles of Sequential Consolidation of Pembrolizumab 200mg every 21 days and then four cycles Nab-paclitaxel 100 mg/mg2 on day 1 and day 8 every 21 days
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Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles. Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.
其他名称:
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有源比较器:Arm B: Sequential Consolidation
Completion of 4 cycles of Sequential Consolidation of Nab-paclitexel 100 mg/m2 on day 1 and day 8 every 21 days and then Pembrolizumab 200 mg every 21
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Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles. Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.
其他名称:
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有源比较器:Arm C: Concurrent Consolidation
Concurrent Consolidation of Nab paclitaxel 100 mg/m2 on day 1 and day 8 plus Pembrolizumab 200 m5 on day 1 every 21 days for four cycles
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Receive Pembrolizumab 200 mg on day 1 every 21 days for four cycles. Receive nab-paclitaxel 100 mg/m2 on day 1 and day 8 every 21 days for four cycles.
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 Survival
大体时间:Up to 60 months
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Overall survival is defined as the time from day 1 of treatment to death from any cause.
Median overall survival was calculated for each arm.
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Up to 60 months
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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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Progression Free Survival (PFS)
大体时间:Up to 60 months
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PFS is defined as the time from first day of treatment until disease progression as defined by the response evaluation criteria in solid tumors (RECIST 1.1) and and Immune Related Response Criteria (irRC), or death from any cause death or progression. RECIST 1.1 Progressive Disease (PD): >= 20% increase in the sum of the LD of the target lesions, Stable Disease (SD) Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, Nonprogressive disease (NPD): No measurable disease at the entrance of the study or otherwise non measurable disease will be assessed for progression. irRC Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment no less than 4 weeks later. |
Up to 60 months
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Overall Rates of Response (ORR)
大体时间:6 months
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ORR is defined as the number of subjects with complete response + partial response based on RECIST 1.1 and irRC criteria. RECIST 1.1 Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >=30% decrease in the sum of the longest diameter (LD) of target lesions. irRC Complete Response (irCR): Disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis, Partial Response (irPR): ≥30% decrease in the sum of target lesions and non-target lesions are irNN. |
6 months
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Rates of Response in Arm A and Arm B
大体时间:6 months
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Rates of Response is defined percent tumor size reduction based RECIST1.1 and irRC criteria (the latter if applicable) after each component of therapy in Arm A and Arm B.
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6 months
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Toxicity Profile
大体时间:6 months
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The toxicity profile is classified and defined by both provider and the participants reported outcomes. Clinician assessed toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) Participants assessed toxicity will be classified based on the Patient-Reported Outcome version of the CTCAE (PRO-CTCAE). Adverse events occurring in greater than two patients or any grade 3 toxicity were included. |
6 months
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Quality of Life (QOL) End of Treatment
大体时间:Baseline to End of Treatment (up to 210 Days)
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Changes in QOL score for each subject are defined as the difference between the baseline, and at end of treatment. QOL will be evaluated using The Functional Assessment of Cancer Therapy-Lung (FACT-Lung) scale at baseline and the end of treatment. The FACT-L is the FACT-G and a lung cancer-specific (LCS) subscale given at baseline and end of treatment. The FACT-G is a 27-item measure of general QOL assessing function in 4 domains: physical well-being, social-family well-being, emotional well-being, and functional well-being. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL. |
Baseline to End of Treatment (up to 210 Days)
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Quality of Life (QOL) 7 Weeks
大体时间:Baseline to 7 weeks (40-50 Days)
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Changes in QOL score for each subject are defined as the difference between the baseline, and at 7 weeks. QOL will be evaluated using The Functional Assessment of Cancer Therapy-Lung (FACT-Lung) scale at baseline and 7 weeks. The FACT-L is the FACT-G and a lung cancer-specific (LCS) subscale given at baseline and at end of treatment. The FACT-G is a 27-item measure of general QOL assessing function in 4 domains: physical well-being, social-family well-being, emotional well-being, and functional well-being. Items are rated by patients on a Likert scale from 0 to 4. Higher scores represent better QOL. |
Baseline to 7 weeks (40-50 Days)
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
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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