ERBITUX® Followed by Adjuvant Treatment With Chemoradiation and ERBITUX® for Locally Advanced Head and Neck Squamous Cell Carcinoma
2018年8月14日 更新者:Robert Ferris
Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma
There are currently no useful tests to identify patients who will respond to cetuximab therapy, notably because EGFR levels do not correlate with the clinical responses observed.
Thus, the investigators are investigating the role of cellular immunity and immune escape mechanisms to explain the differential clinical response to cetuximab.
研究概览
地位
完全的
条件
详细说明
This prospective phase II clinical trial of preoperative, single-agent cetuximab treated patients is being conducted in order to obtain specimens before and after 4 weeks of cetuximab for immune biomarker studies.
Stage III/IV HNC patients will be treated with definitive surgical resection and observed for disease recurrence.
Cetuximab will be administered for a 3-4 week preoperative period to study biomarker modulation in correlation clinical response by CT scan and tumor apoptosis/proliferation after tumor excision, immediately after neoadjuvant cetuximab but before surgery.
We will biopsy the skin/acneiform rash in all patients to correlate rash with biomarker modulation and clinical response.
Cetuximab may also be given in the adjuvant setting.
A primary scientific hypothesis will be tested: does short term pre-operative exposure to cetuximab modulate blood immune biomarkers and is immune modulation associated with anti-tumor effect?
Forty (n=40) patients with complete specimens (tumor, peripheral blood mononuclear cells (PBMC) and serum) are necessary to enable adequate statistical power to be reached using paired specimens.
A secondary set of hypotheses will evaluate the association between pre-operative biomarker levels and modulation with disease recurrence.
The proposed trial will accrue stage II, III or IV surgical candidates without distant metastasis.
研究类型
介入性
注册 (实际的)
40
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
Pennsylvania
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Pittsburgh、Pennsylvania、美国、15232
- UPCI - Hillman Cancer Center
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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:
- Histologically or cytologically confirmed, previously untreated HNC. Clinical stage III or IVA disease without distant metastases as determined by CT, and as defined by the American Joint Committee on Cancer Staging System, Sixth edition (See Appendix I).
- Primary tumors of the oral cavity, oropharynx, hypopharynx, or larynx will be included. Primary tumors of the sinuses, paranasal sinuses, or nasopharynx, or unknown primary tumors are NOT allowed.
- Macroscopic complete resection of the primary tumor must be planned.
- Age greater than or equal to 18 years.
- ECOG performance status 0-1.
Adequate hematologic, renal and hepatic function, as defined by:
- Absolute neutrophil count (ANC) greater than or equal to 1,500/ul, platelets greater than or equal to 100,000/ul.
- Creatinine clearance > 40
- Bilirubin less than or equal to 1.5 x ULN, AST or ALT less than or equal to 2.5 x ULN.
- Have signed written informed consent.
Exclusion Criteria:
- Subjects who fail to meet the above criteria.
- Prior severe infusion reaction to a monoclonal antibody.
- Pregnancy or breastfeeding. Women of childbearing potential (WOCBP) must practice acceptable methods of birth control to prevent pregnancy. Prior to study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. In addition, men enrolled on this study should understand the risks to any sexual partner of childbearing potential and should practice an effective method of birth control.
- All WOCBP MUST have a negative pregnancy test within 7 days prior to first receiving investigational product. If the pregnancy test is positive, the patient must not receive investigational product and must not be enrolled in the study. In addition, all WOCBP should be instructed to contact the Investigator immediately if they suspect they might be pregnant (e.g., missed or late menstrual period) at any time during study participation. The Investigator must immediately notify BMS in the event of a confirmed pregnancy in a patient participating in the study.
- Subjects with an ECOG performance status of 2 or worse.
- Evidence of distant metastasis.
- Any other malignancy active within 5 years except for non-melanoma skin cancer or carcinoma in situ of the cervix, DCIS or LCIS of the breast.
- Prior history of HNC.
- Prior therapy targeting the EGFR pathway.
- Any unresolved chronic toxicity greater than or equal to grade 2 from previous anticancer therapy (except alopecia), according to Common Terminology Criteria for Adverse Events v4.0 (CTCAE).
- Acute hepatitis, known HIV, or active uncontrolled infection.
- History of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within prior 6 months, untreated known coronary artery disease, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
- Uncontrolled peptic or gastric ulcer disease, or gastrointestinal bleeding within prior 6 months.
- Active alcohol abuse or other illness that carries a likelihood of inability to comply with study treatment and follow-up.
- Treatment with a non-approved or investigational drug within 30 days prior to Day 1 of study treatment.
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:Neo-Adjuvant Cetuximab
Neo-Adjuvant Cetuximab + Surgery + Post-Surgical Radiation + Cisplatin (or Carboplatin) NOTE: Based the results of surgery if the treating physician feels patient is not a candidate for chemotherapy, radiation can be given alone or with cetuximab. |
Pre-Surgery: IV, 400 mg/m2 day 1 then 250 mg/m2 alone days 8 and 15; Post-surgery: IV, 250 mg/m2 weekly concurrent with RT
其他名称:
Surgery for tumor
Radiation (2 Gy/d) to min of 60 Gy + max of 66 Gy post-surgery
Cisplatin 30 mg/m2 or carboplatin AUC 1.5-2/week weekly, Concurrent with radiotherapy
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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 |
|---|---|---|
|
NK Cell Activation
大体时间:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment.
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
|
Serum Cytokines Levels
大体时间:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml)
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
|
T Cell Activation
大体时间:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
T cell activation measured at pre-/post-cetuximab exposure
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
大体时间:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients
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Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
|
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Progression-free Survival (PFS)
大体时间:Up to 54 months
|
The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
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Up to 54 months
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Overall Survival (OS)
大体时间:Up to 2 years
|
Number of patients remaining alive.
|
Up to 2 years
|
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Objective Response (Rate)
大体时间:Up to 2 years
|
The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response.
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Up to 2 years
|
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3-year Progression-free Survival (PFS)
大体时间:3 years
|
Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0.
Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir.
|
3 years
|
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Change in Tumor Size
大体时间:Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab.
|
Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)
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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。
调查人员
- 首席研究员:Rober L Ferris, MD, PhD、University of Pittsburgh Med Ctr (UPCI)
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
2011年2月1日
初级完成 (实际的)
2015年11月4日
研究完成 (实际的)
2017年2月14日
研究注册日期
首次提交
2010年10月7日
首先提交符合 QC 标准的
2010年10月7日
首次发布 (估计)
2010年10月8日
研究记录更新
最后更新发布 (实际的)
2018年8月16日
上次提交的符合 QC 标准的更新
2018年8月14日
最后验证
2018年7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.