NCT01313390终止1 期
DORA: A Phase I and Randomized Phase II Study of Docetaxel and RAD001 (Everolimus) in Advanced/Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 2
- 主要终点
- Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
研究概览
简要总结
RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving everolimus together with docetaxel is more effective than giving docetaxel alone in treating patients with head and neck cancer.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus given together with docetaxel in treating patients with recurrent, locally advanced, or metastatic head and neck cancer.
详细描述
OBJECTIVES:
Primary
- To determine the safety and tolerability of the combination of everolimus and docetaxel in treating patients with recurrent, locally advanced or metastatic squamous cell carcinoma of the head and neck. (Phase I)
- To determine the maximum-tolerated dose and recommended phase II dose of everolimus when combined with docetaxel in these patients. (Phase I)
- To examine the response rates in patients receiving the combination of docetaxel and everolimus and those receiving docetaxel alone. (Phase II)
Secondary
- To investigate possible pharmacokinetic interactions between docetaxel and everolimus in these patients. (Phase I)
- To investigate the effect of everolimus on downstream targets of mTOR in tumor in these patients. (Phase I)
- To examine the time to progression after docetaxel and everolimus in these patients. (Phase II)
- To perform a pilot study to attempt to identify predictors of response, including evaluation of EGFR family member expression, mutations, or amplifications. (Phase II)
- To attempt to identify downstream targets of the EGFR pathway including phosphorylation of S6 and phosphorylation of AKT. (Phase II)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed squamous cell carcinoma of the head and neck
- •Locally advanced or metastatic disease
- •No patients with locally advanced disease for whom radiotherapy is indicated
- •Recurrent disease
- •Incurable disease
- •Measurable disease by RECIST criteria
- •Recurrent disease within a prior radiation field can be considered to be measurable
- •Patients may have received 1 line of prior chemotherapy (but not a taxane) for locally advanced or metastatic disease
- •Patients may have received prior radiation therapy for locally advanced or metastatic disease (but must have completed the radiotherapy > 6 months before recruitment)
- •No disease relapsed within 6 months of radiotherapy
- •No evidence of central nervous system metastases
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-1
- •Life expectancy ≥ 12 weeks
- •Absolute neutrophil count ≥ 1,500/mm³
- •Platelet count ≥ 100,000/mm³
- •Hemoglobin ≥ 10 g/dL
- •Urea and creatinine normal
- •Serum bilirubin normal
- •AST or ALT ≤ 1.5 times upper limit of normal (ULN)
- •Alkaline phosphatase < 2.5 times ULN
- •Negative pregnancy test
- •Not pregnant or nursing
- •Fertile patients must use effective contraception during and for 3 months (female) or 2 months (male) after the last dose of the study treatment
- •No uncontrolled infection
- •No mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study
- •No prior malignancy likely to interfere with the patient's ability to comply with treatment and/or follow up
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •No prior chemotherapy for any cancer, except for head and neck cancer
- •No prior taxane
- •No prior therapy with any erbB inhibitors (except cetuximab given with radiotherapy, as indicated in treatment algorithm)
- •More than 6 months since prior radiotherapy for locally advanced or metastatic disease
- •At least 4 weeks since prior investigational drug
- •No concurrent use of drugs known to inhibit CYP3A4 (except dexamethasone), or block P-glycoprotein, including grapefruit juice
- •No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, radiotherapy, or experimental medications
- •No concurrent live vaccines during everolimus therapy
排除标准
- 未提供
结局指标
主要结局
Maximum-tolerated dose and recommended phase II dose of everolimus in combination with docetaxel (phase I)
Safety and tolerability of the combination of everolimus and docetaxel
Response using RECIST criteria (phase II)
次要结局
- Pharmacokinetic profile of docetaxel with and without concurrent everolimus (phase I)
- Pharmacokinetic profile of everolimus with and without concurrent docetaxel (phase I)
- Time to progression following response (time from treatment start to tumor progression as defined by RECIST criteria) (phase II)
- Mutations in EGFR1, AKT, mTOR, ras, or p53 to be tested on paraffin-embedded tissue from the primary or secondary tumor; results to be correlated with outcome (phase II)
- Amplifications of EGFR1 and bcl2 expression to be tested by FISH and immunostaining on paraffin-embedded tissue from primary tumor; results to be correlated with outcome (phase II)
研究者
研究点 (2)
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