Addition of Decitabine to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Phase 2-3, Open-label, Randomised Controlled Trial
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 500
- 试验地点
- 1
- 主要终点
- Progression-free survival in DTC treated advanced ovary cancer
研究概览
简要总结
Ovarian cancer is the most lethal gynecological cancer and the 5th leading cause of cancer death in women. Most patients are typically diagnosed with advanced-stage disease. Platinum-paclitaxel regimen has been widely adopted as a standard first-line treatment for advanced ovarian cancer. Multiple collaborative randomised phase III trials evaluating the addition of a third chemotherapy agent, maintenance therapy or alternative taxanes failed to demonstrate significant improvements over a standard carboplatin/taxane doublet.
Decitabine (DAC), one major DNA demethylating agent, has been approved for treatment of preleukemic hematological disease myelodysplastic syndrome (MDS) by the Food and Drug Administration. Past trials of these with high doses, i.e., the use of maximal tolerated dose, for patients with solid tumors showed a low therapeutic index, due to extreme toxicities that have probably confounded the ability to document the true clinical response.
Low dose DNA demethylation agent decitabine (DAC) can resensitize the therapeutic indexes of resistent ovary cancer cells in vivo and in vitro.
The investigators hypothesized that DAC-triggered epigenetic reprogramming of tumor cells and possible immune cells could induce pronounced long-dated clinical effect by chemosensitization- and immunopotentiation-driven maximal eradicating roles on the minimal/residual lesions in primary patients with poor prognosis.
详细描述
Given the poor prognosis and the currently existed therapeutic strategies, The investigators will perform a prospective, randomized, phase II to III, intergroup trial to compare carboplatin plus paclitaxel (TC) with the DAC-primed TC (DTC) regimen in previously untreated patients with stage II to IV ovarian cancer.
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 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stages II to IV fallopian tube cancer, or primary peritoneal cancer. If only the results of cytological examinations were available, patients needed to have the following criteria: a cytological diagnosis of adenocarcinoma; an abdominal mass more than 2 cm in diameter on abdominal images; and a CA125 to carcinoembryonic antigen (CEA) ratio10 of more than 25, or no evidence of gastrointestinal cancer if CA125/CEA ratio was less than or equal to
- •Previous chemotherapy was not allowed.
- •All patients had to be at least 18 years of age, to have an Eastern Cooperative
- •Oncology Group (ECOG) performance status of 0-3, and were required to have adequate hematologic, renal, and hepatic function.
排除标准
- •Patients were excluded if they had an ovarian tumour with a low malignant potential, or synchronous or metachronous (within 5 years) malignant disease other than carcinoma in situ.
研究组 & 干预措施
DTC Arm
Patients are randomly assigned to receive lower-dose decitabine treatment followed by TC regimen (ie, DTC arm).
干预措施: Decitabine (DTC Arm) (Drug)
TC regimen
Patients were randomly assigned to receive carboplatin plus paclitaxel (ie, TC arm).
干预措施: Paclitaxel and Carboplatin (TC Arm) (Drug)
结局指标
主要结局
Progression-free survival in DTC treated advanced ovary cancer
时间窗: up to 20 months
The primary endpoint of this trial was progression-free survival (PFS), defined as the time from the date of randomisation to the date of the first occurrence of any of the following events: appearance of any new lesions that could be measured or assessed clinically; or CA125 criteria of disease progression. For patients with measurable disease, clinical or radiographical tumour measurements had priority over CA125 levels, and progression during treatment could not be declared on the basis of CA125 alone.
Overall survival rate in DTC treated advanced ovary cancer
时间窗: 30 months
Overall survival (OS), defined as the time from random assignment to death as a result of any cause, response rate, and adverse events.response to treatment, toxicity, and quality of life. Toxicities were evaluated per course and per patient (worst score over all courses).
Overall response rate in DTC treated advanced ovary cancer
时间窗: 1 year
Tumor measurements were made before each cycle by physical examination, before every third cycle by imaging methods in patients with measurable or evaluable disease, and after the last cycle. The same tumor assessment methods that were employed for baseline measurement were used for each repeat evaluation. Tumor response was graded according to Response Evaluation Criteria in Solid Tumors (RECIST).
Toxicity in DTC treated advanced ovary cancer
时间窗: 8 months
Adverse events and toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NIC-CTC). Toxicities were recorded continuously; blood chemistry parameters were measured before each treatment cycle and weekly thereafter.Quality of life was assessed with the use of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-OV28 questionnaires.
次要结局
- Pharmacokinetics of lower-dose decitabine(up to 8 weeks)
研究者
Han weidong
professor
Chinese PLA General Hospital