A Cancer Research UK Randomised, Multicentre, Phase II Trial of the DNAhypomethylating Agent, 5-Aza-2'-Deoxycytidine (Decitabine) Given Intravenously in Combination With Carboplatin, Versus Carboplatin Alone Given 4 Weekly in Patients With Progressive, Advanced Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 134
- 试验地点
- 11
- 主要终点
- Response rate (partial response [PR] or complete response [CR]) in patients with methylated hMLH1 DNA in plasma as measured by RECIST criteria or CA-125 criteria
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as carboplatin and decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether carboplatin is more effective with or without decitabine in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
PURPOSE: This randomized phase II trial is studying carboplatin and decitabine to see how well they work compared with carboplatin alone in treating patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
详细描述
OBJECTIVES:
Primary
- To compare the response rate in patients with progressive, advanced ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer who have methylated hMLH1 DNA in plasma treated with carboplatin with vs without decitabine.
Secondary
- To compare the response rate in all patients (regardless of methylation status) treated with these regimens.
- To compare the progression-free survival and overall survival of patients treated with these regimens.
- To compare the safety and tolerability of these regimens.
- To determine the feasibility of combining decitabine with carboplatin.
- To determine the incidence of hypersensitivity reactions to carboplatin.
- To study the relationship between peak plasma levels of decitabine and global or CpG island specific methylation.
- To study the relationship between global and gene specific methylation in peripheral blood mononuclear cells and response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm I
Patients receive carboplatin IV over 30-60 minutes on day 1.
干预措施: carboplatin (Drug)
Arm II
Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.
干预措施: carboplatin (Drug)
Arm II
Patients receive decitabine IV over 6 hours on day 1 and carboplatin IV over 30-60 minutes on day 8.
干预措施: decitabine (Drug)
结局指标
主要结局
Response rate (partial response [PR] or complete response [CR]) in patients with methylated hMLH1 DNA in plasma as measured by RECIST criteria or CA-125 criteria
次要结局
- Response rate (PR or CR) in all patients (regardless of methylation status) as measured by RECIST criteria or CA-125 criteria
- Progression-free survival and overall survival
- Adverse events as measured by NCI CTCAE v3.0
- Correlation between response (PR or CR) and global and CpG island specific DNA methylation in peripheral blood mononuclear cells
- CpG island specific DNA methylation in tumor DNA and expression of genes as measured by RNA or protein assays
- Correlation between peak plasma levels of decitabine and global and CpG island specific DNA methylation in peripheral blood mononuclear cells
- Correlation between response (PR, CR, or stable disease) and CpG island specific DNA methylation in tumor DNA and expression of genes by RNA or protein assays
- Immunoassays of proteins in plasma
- Total dose and dose intensity of carboplatin and decitabine
- Incidence of grade 3-4 hypersensitivity reactions
- CpG island specific DNA methylation in plasma and tumor DNA
- Correlation between response (PR or CR) and CpG island specific DNA methylation in plasma DNA
- CpG island specific DNA methylation in tumor DNA