Phase II Study of Azacitadine and Entinostat in Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 14
- 主要终点
- Confirmed Tumor Response
研究概览
简要总结
This phase II trial is studying how well giving azacitidine together with entinostat works in treating patients with metastatic colorectal cancer. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the preliminary efficacy via Response Evaluation Criteria In Solid Tumors (RECIST) response rate of the combination of azacitidine and entinostat in patients with metastatic colorectal cancer.
SECONDARY OBJECTIVES:
I. Explore the effects of azacitidine and entinostat on time to progression in patients with metastatic colorectal cancer.
II. To assess the toxicity for combination azacitidine and entinostat therapy.
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 confirmed metastatic colorectal cancer
- •Measurable disease
- •Patient has failed ≥ 2 prior chemotherapy regimens
- •Not a candidate for curative resection
- •No CNS metastases within ≤ 2 years
- •Treatment for brain metastasis and whole brain disease that has remained stable for > 3 months allowed
- •Patients who have not been treated with steroid therapy may be allowed
- •ECOG performance status 0-1
- •Life expectancy ≥ 12 weeks
- •Leukocytes ≥ 3,000/mm^3
- •ANC ≥ 1,500/mm^3
- •Platelet count ≥ 100,000/mm^3
- •Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- •AST and ALT ≤ 2.5 times ULN
- •Creatinine normal OR creatinine clearance ≥ 60 mL/min
- •Negative pregnancy test
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •Sensory neuropathy ≤ grade 2 allowed
- •Willing to provide tissue and blood samples
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, azacitidine, mannitol, or other agents used in the study
- •No uncontrolled intercurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •NYHA class II-IV symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness and/or social situations that would limit compliance with study requirements
- •No history of severe bleeding without thrombocytopenia
- •No concurrent radiotherapy including palliative treatment
- •Toxicities from prior therapy have resolved to ≤ grade 1
- •More than 4 weeks since prior chemotherapy (> 6 weeks for nitrosoureas or mitomycin C)
- •More than 4 weeks since prior major surgical procedure
- •No prior histone deacetylase inhibitors (including valproic acid) or demethylating agents
- •No concurrent investigational agents
- •No concurrent combination antiretroviral therapy in HIV-positive patients
- •No concurrent investigational or commercial anticancer agents or therapies
排除标准
- 未提供
研究组 & 干预措施
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: entinostat (Drug)
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: azacitidine (Drug)
Treatment (entinostat, azacitidine)
Patients receive azacitidine subcutaneously on days 1-5 and 8-10 and oral entinostat on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
结局指标
主要结局
Confirmed Tumor Response
时间窗: At 6 month evaluation
Each evaluable patient is classified as having a confirmed tumor response if they have either a complete response (CR) or partial response (PR) lasts at least 4 weeks. Tumor response is measured by using RECIST v1.1 (Response Evaluation Criteria in Solid Tumors). A CR is defined as a disappearance of all target lesions, and each target lymph node must have reduction in short axis to \<1.0 cm. A PR is defined as a 30% decrease in the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation, compared to pre-treatment measurements. The confirmed response rate is calculated as the number of confirmed CR+PR, divided by the total number of evaluable patients, with 95% confidence intervals estimated using the approach of Duffy and Santner.
次要结局
- Time to Progression(From the start of treatment to the earliest of the date documenting disease progression, assessed up to 3 years)