Randomized, Double-Blind, Phase III Trial of Chemotherapy Plus the Transcriptional Therapy Hydralazine and Magnesium Valproate Versus Chemotherapy Plus Placebo in Cisplatin-Resistant Recurrent Ovarian Cancer.
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 211
- 试验地点
- 1
- 主要终点
- Progression-Free Survival
研究概览
简要总结
The current standard for recurrent, persistent or metastatic cisplatin-resistant ovarian cancer is palliative chemotherapy with either topotecan, liposomal doxorubicin or gemcitabine, however, the results need to be improved. Epigenetic aberrations play an important role in cancer progression by silencing growth regulatory genes and there is now evidence that inhibitors of DNA methylation and HDAC inhibition synergize the cytotoxicity of chemotherapy.
Objective. To determine the superiority of epigenetic therapy with hydralazine and valproate plus topotecan over placebo plus topotecan upon progression-free survival.
Hypothesis. Hydralazine and magnesium valproate associated to topotecan will increase progression-free survival from 6 to 9 months as compared with the same regimen of chemotherapy plus placebo.
详细描述
Randomized, double-blind phase III trial. A total of 211 patients (alpha 0.5, power 0.8)with cisplatin-resistant recurrent or persistent cancer will be randomized to topotecan + placebo or topotecan + hydralazine + valproate for 6 courses every 4 weeks. Patients will receive an oral dose of hydralazine of 182mg (rapid) or 83mg (slow) according to the acetylator phenotype in a single daily dose and magnesium valproate at an oral dose of 40mg/Kg t.i.d. Both drugs in a slow-release formulation. Experimental drugs or placebo will start from seven days before day 1 of chemotherapy until the end of the sixth course.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Measurable or evaluable disease(evaluable according to CA125 criteria of GCIG) Cisplatin resistant ovarian cancer
- •Persistent or progression to first line platinum-based chemotherapy
- •Relapse within 6 months after completing first line platinum-based chemotherapy
- •Platinum-sensitive disease who are failed to second line therapy based on platinum.
- •Adequate organic function as defined by: hemoglobin >10 g/L, leukocytes >4000/mm3, platelets >100 000mm3; normal creatinine value and creatinine clearance >60 mL/min; total bilirubin < 1.5 upper normal limit value
排除标准
- •History of allergy to hydralazine or valproate;
- •Past or present condition of rheumatic disease, central nervous system disease, heart failure from aortic stenosis and postural hypotension as diagnosed by a physician;
- •Newly diagnosed hypertension patients with or without pharmacological treatment are allowed as long as their treatment do not include hydralazine.
- •Previous use of the experimental drugs (hydralazine and magnesium valproate) as well as if patients were pregnant or breast-feeding.
- •Other exclusion criteria are uncontrolled systemic disease or infection.
研究组 & 干预措施
1
Topotecan hydralazine valproate
干预措施: Hydralazine and magnesium valproate (Drug)
2
Placebo, hydralazine, valproate
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-Free Survival
时间窗: 2-years
次要结局
- Safety, response, overall survival.(2-years)