Inhibition of DNA Methylation by 1-Hr Infusion of 5-aza-2'-Deoxycitidine (Decitabine) x 10 Days (M-F) With Escalating Doses of Sub-Q Pegylated (PEG) Interferon-alpha 2B (PEG-Intron): A Phase I Study With Molecular Correlates
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
研究概览
简要总结
This phase I trial is studying the side effects of decitabine when given together with or without interferon alfa-2b, and the best dose of interferon alfa-2b, in treating patients with unresectable or metastatic solid tumors. Drugs used in chemotherapy, such as decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as interferon alfa-2b, may stimulate the immune system in different ways and stop tumor cells from growing. It is not yet known whether decitabine is more effective when given with or without interferon alfa-2b in treating solid tumors.
详细描述
PRIMARY OBJECTIVES:
I. To assess toxicities of decitabine plus escalating doses of pegylated interferon alfa-2b (PEG-Intron) in patients with metastatic solid tumor.
II. To identify the dose-limiting toxicity of decitabine in combination with escalating doses of pegylated interferon alfa-2b in these patients.
III. To identify the maximum tolerated dose of pegylated interferon alfa-2b in combination with decitabine in these patients.
SECONDARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Biopsy-proven solid tumor
- •Metastatic or unresectable disease
- •Tumor amenable to biopsy
- •No curative or more effective treatment for this disease exists, in the opinion of the investigator
- •Measurable disease by scans as assessed by RECIST criteria
- •No untreated brain metastasis
- •No longer receiving steroid therapy for previously treated brain metastasis
- •Zubrod performance status of 0-2
- •Bilirubin ≤ 1.5 times upper limit normal (ULN)
- •SGOT or SGPT ≤ 2.5 times ULN (≤ 5 ULN if hepatic metastases present)
- •Serum creatinine ≤ 1.5 times ULN
- •Creatinine clearance ≥ 50 mL/min
- •ANC > 1,500/μL
- •Platelet count > 100,000/μL
- •Hemoglobin > 9 g/dL (transfusion allowed)
- •No NYHA class III-IV cardiac problems (e.g., congestive heart failure or myocardial infarction within the past 2 months)
- •No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective barrier contraception during and for 3 months after completion of study therapy
- •Willing to undergo biopsies
- •No medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete the treatment, or to grant reliable informed consent
- •No other prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I, II, or III cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
- •No prior extensive pelvic irradiation or prolonged nucleoside analogue pretreatment
- •At least 28 days since prior and no concurrent chemotherapy, radiotherapy, surgery, biological therapy, anticancer agent, or other investigational drug
排除标准
- 未提供
研究组 & 干预措施
Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients whose disease is not responding after the first course may crossover to group 2.
干预措施: decitabine (Drug)
Group 1 (chemotherapy)
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients whose disease is not responding after the first course may crossover to group 2.
干预措施: laboratory biomarker analysis (Other)
Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: peginterferon alfa-2b (Biological)
Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: decitabine (Drug)
Group 2 (chemotherapy and antineoplastic agent)
Patients receive decitabine as in group 1 and pegylated interferon alfa-2b subcutaneously on days 1, 8, 15, and 22. 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
Toxicities as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
时间窗: Up to 28 days
The type, frequency, and severity of each toxicity will be reported.
Dose-limiting toxicity (DLT) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
时间窗: First 28-day course
DLT is defined as grade III drug-related non hematologic and/or grade IV drug-related hematologic toxicity.
Maximum-tolerated dose (MTD) of pegylated interferon alfa-2b when given with decitabine as assessed by NCI CTCAE version 3.0
时间窗: First 28-day course
The MTD will be the dose level where not more than 1 case of a specific grade III-IV drug-related toxicity is observed, and either 2+toxicities have been observed at the next highest dose level, or the maximum dose-level of PEG-Intron has been reached.
次要结局
- Global (genomic) DNA methylation changes by high-performance liquid chromatography (HPLC)(Baseline to up to day 1 of course 2)
- Changes in expression of methylation-regulated genes in human biological tissues(Baseline to up to day 1 of course 2)
- Complete and partial response rates(Up to 1 year)