Phase I/II Clinical Trial of Combined Pre-Irradiation With Pemetrexed and Erlotinib Followed by Maintenance Erlotinib for Recurrent and Second Primary Squamous Cell Carcinoma of the Head and Neck
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 27
- 试验地点
- 2
- 主要终点
- Progression-free Survival (PFS) at 1 Year (Phase II)
研究概览
简要总结
RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs, such as pemetrexed and erlotinib, may make tumor cells more sensitive to radiation therapy. Erlotinib and pemetrexed may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving intensity-modulated radiation therapy together with pemetrexed and erlotinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of erlotinib when given together with intensity-modulated radiation therapy and pemetrexed and to see how well they work in treating patients with recurrent or second primary head and neck cancer.
详细描述
OBJECTIVES:
Primary
- Evaluate the acute toxicity and feasibility of intensity modulated radiotherapy (IMRT) in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in patients with recurrent or second primary squamous cell carcinoma of the head and neck. (Phase I)
- Determine the maximum tolerated dose and recommended phase II dose of erlotinib hydrochloride in these patients. (Phase I)
- Determine progression-free survival (PFS) at 1 year in these patients. (Phase II)
Secondary
- Determine median PFS, median overall survival (OS), and OS at 1 and 2 years in these patients.
- Determine objective tumor response as measured by CT scan or MRI in these patients.
- Evaluate the acute and chronic toxicity of IMRT in combination with radiosensitizing drugs pemetrexed disodium and erlotinib hydrochloride in these patients.
- Evaluate the impact of treatment on quality of life as measured by FACT-H&N, PSS-HN, MD Anderson Dysphagia Inventory (MDADI), and swallowing by direct functional measurements at different time points.
- Evaluate the level of phosphorylation of different tyrosine residues within the cytoplasmic domain of EGFR, bound adaptors, as well as markers of downstream pathways activation by nano LC-MS/MS in tumor tissue and correlate with levels of P-AKT and P-ERK by immunohistochemistry and with response to treatment.
- Measure the levels of TS and p53 and correlate with treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Erlotinib
Erlotinib
干预措施: erlotinib hydrochloride (Drug)
Erlotinib
Erlotinib
干预措施: pemetrexed disodium (Drug)
Erlotinib
Erlotinib
干预措施: quality-of-life assessment (Procedure)
Erlotinib
Erlotinib
干预措施: intensity-modulated radiation therapy (Radiation)
结局指标
主要结局
Progression-free Survival (PFS) at 1 Year (Phase II)
时间窗: 1 year
Determine Progression Free Survival at 1 year defined as the percentage of patients who are alive at 1 year after beginning of their concurrent re-irradiation and chemotherapy without loco-regional progression of their disease as measured by CT scan or MRI.
Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
时间窗: 56 Days
Dose at which 100% of participants tolerated the dose
次要结局
- Median Overall Survival(up to 5 years)
- Overall Survival(1 and 2 years)
- Change in Quality of Life- FACT H&N(baseline and 12 months)
- Change in Quality of Life: MDADI(baseline and 12 months)
- Objective Tumor Response(1 year)
- Median Progression Free Survival(2 years)
- Evaluation of Acute and Chronic Toxicity(1 year)
- Evaluation of Biomarkers(throughout study completion, up to 2 years)
- Change in Quality of Life: PSS-HN(baseline and 6 months)