Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
A Phase II Trial of Postoperative Radiation, Cisplatin, and Panitumumab in Locally Advanced Head and Neck Cancer
The objectives for this study is as follows:
Primary:
- To evaluate the progression-free survival of locoregionally advanced (stages III/IV) SCCHN patients undergoing postoperative chemoradiotherapy with panitumumab.
Secondary:
- To evaluate the overall survival, event-free survival, and toxicities.
- To correlate efficacy parameters with 1) EGFR and downstream pathway activation, 2) FcyR polymorphisms, and 3) serum cytokine profiles. More specifically, the aim is to demonstrate the usefulness of biomarkers (downstream signaling molecules, FcyR polymorphisms, or tumor and serum cytokine(s) in predicting progression-free survival in patients with SCCHN treated with the above treatment. Specific biomarkers that relate to Epidermal Growth Factor Receptor and angiogenesis, including EGFR, pEGFR, Src, pMAPK, pSTAT3, pSTAT5, pSTAT1, pAKT, p38, p21, p27, PARP, E-cadherin, p-ErbB3, Ki67, VEGF, and IL-8, using reverse phase protein microarrays (RPPA) will be tested in baseline archival paraffin-embedded tumor tissue. To collect tumor tissue from pretreatment biopsies for cytokine/chemokine and immune biomarker studies on tumor tissue. We plan to investigate the expression of pAKT, pMAPK, and other EGFR pathway-related markers as well angiogenesis biomarkers. In addition, EGFR polymorphisms will be studied in tumor tissue samples and serum. Additional studies may be performed in the future. Some of these studies may be performed by Amgen.
研究概览
地位
条件
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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Pennsylvania
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Pittsburgh、Pennsylvania、美国、15232
- University of Pittsburgh 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:
- Pathologically staged squamous cell carcinoma of the head and neck, stage III or IVa (AJCC 6th edition 2002) of the oral cavity, larynx, or hypopharynx that is status post potentially curative surgical resection without gross residual tumor, except the following: a)T3N0 laryngeal primary and b) any T1N1, if there are no high-risk pathologic features (high risk defined as positive margins, extracapsular spread, and perineural or angiolymphatic invasion).
- Patients should not have gross residual disease.
- No prior chemotherapy, biologic/targeted therapy (including any prior therapy which specifically and directly targets the EGFR pathway), or radiotherapy for head and neck cancer. A brief course, up to 2 weeks, of prior neoadjuvant single-agent biologic/targeted therapy of any type (except EGFR monoclonal antibodies) prior to surgical resection is permitted.
- No more than 6 7 weeks (minimum of 3 weeks) should have elapsed between surgery and initiation of radiation.
- No prior radiation or chemotherapy for head and neck cancer.
- ECOG performance status of 0-1
- Patients must have normal organ and marrow function Absolute neutrophil count >/=1,500/uL Platelets >/=100,000/uL Hemoglobin >/= 10 g/dL Total bilirubin <1.5 x normal institutional limits Creatinine clearance > 60 mL/min
- No prior invasive malignancy unless the DFS is 3 years or more.
- Age > 18 years.
- Pregnant or breast-feeding women are excluded (see exclusion criteria).
- Informed consent must be obtained from all patients prior to beginning therapy. Patients should have the ability to understand and the willingness to sign a written informed consent document.
- Patients who have tumor tissue available from previous diagnostic or therapeutic procedures should submit the specimen for assessment of EGFR and related biomarkers after signing informed consent.
Exclusion Criteria:
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements. Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, recent myocardial infarction (within prior 6 months), uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction. All patients will have a baseline EKG. If abnormalities consistent with active coronary artery disease are detected, the patient will be referred to a cardiologist for appropriate evaluation and management prior to treatment on study.. Patients with history of hypertension must be well-controlled upon study entry (≤150/90) on a stable regimen of anti-hypertensive therapy. Patients should not have any prior history of hypertensive crisis or hypertensive encephalopathy.
- Patients may not be receiving any other investigational agents.
- No history of prior malignancy, with the exception of curatively treated squamous cell or basal carcinoma of the skin or in situ cervical cancer, or malignancy that has been treated with a curative intent with a 3-year disease-free survival.
- No patients with significant baseline sensory or motor neurologic deficits(> grade I neuropathy) will be treated on this study.
- Pregnant women are excluded from this study because chemotherapy and radiation therapy have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with chemotherapy, breastfeeding should be discontinued if the mother is treated with chemotherapy.
- Prior to study enrollment, women of childbearing potential (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 urine pregnancy test at baseline, or within 7 days prior to receiving investigational product. The minimum sensitivity of the pregnancy test must be 25 IU/L or equivalent units of HCG. If the urine pregnancy test is positive, a serum pregnancy test will then be performed to confirm the result. In the event that both the urine and serum pregnancy tests are positive, the subject 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 Amgen in the event of a confirmed pregnancy in a patient participating in the study.
-Prior severe infusion reaction to a human monoclonal antibody.
学习计划
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 |
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实验性的:Panitumumab, Cisplatin plus radiation
Standard radiation 60-66 Gy with 200 cGy daily fractions in 6-7 weeks Cisplatin* 30 mg/m2 IV, weekly during radiation (total of 6-7 doses based upon radiation therapy dose requirements) Panitumumab 2.5 mg/Kg IV, weekly during radiation (total of 6-7 doses based upon radiation therapy dose requirements)
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Panitumumab, starting dose, 2.5mg/kg will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation and chemotherapy for 6 weeks; treatment takes about an hour. The panitumumab dose will be calculated based on the subject's actual weekly body weight
其他名称:
Cisplatin, 30 mg/m2 will be given as an intravenous infusion (IV) through a vein in your arm, once a week before radiation therapy and after panitumumab for 6 weeks; treatment takes about an hour
其他名称:
Radiation Therapy 60-66 Gy/200 cGy/daily, five days a week, Monday through Friday, except on weekends and holidays, for six weeks; treatments take about 20 minutes. Radiation will be administered either prior to chemo treatment or after chemo treatment as long as radiation is given on the same day. |
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
---|---|
Probability of Progression-free Survival (PFS) at 2 Years
大体时间:Up to 90 months for cohort; individual patients up to 24 months after study treatment
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Up to 90 months for cohort; individual patients up to 24 months after study treatment
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次要结果测量
结果测量 |
大体时间 |
---|---|
Probability of 2-year Overall Survival
大体时间:Up to 90 months for cohort; individual patients up to 24 months
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Up to 90 months for cohort; individual patients up to 24 months
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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
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