Phase 1/2 Study of Vorinostat in Combination With Radiation Therapy and Infusional 5-FU in Patients With Locally Advanced Adenocarcinoma of the Pancreas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy.
研究概览
简要总结
The durg vorinostat (Zolinza) is a type of drug called an histone deacetylase (HDAC) inhibitor. It inhibits a group of enzymes called histone deacetylases. These enzymes help cancer cells survive. By inhibiting these enzymes, vorinostat helps kill cancer cells. In this research study vorinostat will be given along with radiation therapy and the drug 5-FU. This is the first research study in which vorinostat will be given along with radiation therapy and 5-FU. The purpose of this research study is to find the highest dose of vorinostat that can be given safely along with radiation therapy and 5-FU. The investigators will also begin to get information about whether vorinostat combined with radiation and 5-FU may help to treat pancreatic cancer.
详细描述
- Since we are looking for the highest dose of vorinostat that can be administered safely without severe or unmanageable side effects, not everyone who participates will receive the same dose. The dose will depend upon the number of participants enrolled on the study and how well they have tolerated their doses.
- 5-FU will be given intravenously over 24 hours 7 days per week during each week of radiation therapy. In order for participants to be able to receive the 5-FU as an outpatient, they will need to have central line catheter placed.
- Radiation therapy will be given once per day, 5 days per week, for 6 weeks.
- Vorinostat is taken orally.
- Participants will be seen once per week during the 6 weeks that they are receiving 5-FU, radiation therapy and vorinostat.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically proven adenocarcinoma of the pancreas
- •Evaluable disease
- •Must have received 3-4 months of gemcitabine-based chemotherapy and have had stable disease by RECIST criteria. Regimens include:
- •gemcitabine alone
- •gemcitabine and erlotinib
- •gemcitabine and oxaliplatin
- •gemcitabine and cisplatin
- •gemcitabine and capecitabine
- •18 years of age or older
- •Life expectancy of greater than 4 months
- •ECOG Performance Status 0-1
- •Normal organ and marrow function as outlined in the protocol
- •Ability to drink at least 2 liters of fluid daily
- •Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation
- •Patients must be able to swallow capsules
排除标准
- •Chemotherapy within 3 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Participants may not be receiving any other study agents
- •Known distant metastases to any organ
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or 5-FU
- •Patients taking warfarin due to potential interactions of both 5-FU and vorinostat. Low molecular weight heparin should be substituted when appropriate
- •Patients who have received upper abdominal radiation therapy which fields would overlap with that determined necessary to treat the primary tumor.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Pregnant or breastfeeding women
- •Individuals with history of a different malignancy are ineligible unless they are deemed by the investigator to be at low risk of recurrence of that malignancy. Patients may not have a concurrent second malignancy.
- •Active HIV or hepatitis
- •Prior exposure to HDAC inhibitor (except valproic acid, provided there is a 30 day washout period)
研究组 & 干预措施
Vorinostat, 5-FU, Radiation Therapy
Vorinostat at varying doses; orally, days 1-7, weeks 1-6 5-FU 225 mg/m2/day; intravenous; days 1-5, weeks 1-6 until completion of radiation therapy; Radiation therapy; 180cGy daily Monday-Friday; 28 days of treatment (6 weeks)
干预措施: Radiation therapy (Radiation)
Vorinostat, 5-FU, Radiation Therapy
Vorinostat at varying doses; orally, days 1-7, weeks 1-6 5-FU 225 mg/m2/day; intravenous; days 1-5, weeks 1-6 until completion of radiation therapy; Radiation therapy; 180cGy daily Monday-Friday; 28 days of treatment (6 weeks)
干预措施: 5-FU (Drug)
Vorinostat, 5-FU, Radiation Therapy
Vorinostat at varying doses; orally, days 1-7, weeks 1-6 5-FU 225 mg/m2/day; intravenous; days 1-5, weeks 1-6 until completion of radiation therapy; Radiation therapy; 180cGy daily Monday-Friday; 28 days of treatment (6 weeks)
干预措施: Vorinostat (Drug)
结局指标
主要结局
Maximally Tolerated Dose (MTD) of Vorinostat in Combination With Infusional 5-FU and Radiation Therapy.
时间窗: 6 weeks
The maximum tolerated dose (MTD) is defined as one dose level below the dose level at which participants experience an unacceptable rate of dose-limiting toxicity.
Progression Free Survival (PFS) at 7 Months From Registration
时间窗: 7 months
Progression free survival was defined as the duration of time from registration on study to time of objective disease progression. Death was regarded as a progression event. Progression was defined by the Response Evaluation Criteria in Solid Tumors (RECIST) as at least a 20% increase in the sum of the longest diameter of target lesions, or the appearance of one or more new lesions as seen on radiologic evaluation.
次要结局
- Progression Free Survival(2 years)
- Number of Participants Experiencing Unacceptable Toxicity(1 year)
- Overall Survival(1 year)
- Response Rate(1 year)
- Resectability Rate(5 months)
研究者
Lawrence S. Blaszkowsky, MD
Assistant Physician
Massachusetts General Hospital