Oral Metronomic therapy (OMT) versus treatment of physicians choice(TPC) chemotherapy in platinum resistant advanced ovarian cancer: a randomized controlled study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- median progression free survival
研究概览
简要总结
Advanced epithelial ovarian cancer has dismal outcomes. Worst is the case with “Platinum refractory disease” (PROC), those relapsing within 6 months of platinum-based chemotherapy, with poor response to further chemotherapy and a median survival of<1 year. The current standard of care for PROC is single-agent non-platinum-based chemotherapy. Previous research from our institute showed that the 3-drug combination (Pazopanib+ Cyclophosphamide+Etoposide) could be a novel oral metronomic therapy (OMT) for PROC. [PMID :32048620,34088513]. Our proposal is the next obvious step, to compare this OMT with standard IV chemotherapy in a randomized study. If found superior, OMT will be a new line of therapy, an extremely affordable and acceptable option.
This will be a randomized phase-III, superiority trial, with a parallel design and 1:1 randomization. Patients, with platinum-resistant ovarian cancers will be randomized to the two arms i.e, the Standard of care arm ( IV chemotherapy of physician’s choice which can be either of weekly Paclitaxel, liposomal doxorubicin or weekly Irionotecan) and the Intervention Arm (Oral Metronomic chemotherapy comprising of 3 drugs : Tab Pazopanib 400mg daily, Tab Cyclophosphamide 50mg D1-D28, Cap Etoposide 50mg D1-D10.
Our primary objective is to compare the median progression-free survival ( mPFS) on the OMT arm (experimental arm) versus IV chemotherapy of physician choice (standard of care arm) for the intent-to-treat (ITT) population. Our Secondary objectives are a) To compare the median overall survival (mOS) on the OMT arm (experimental arm) versus IV chemotherapy (standard of care arm) for the ITT population, b) To compare the objective response rates (ORR) for the two arms of the study at 4 months, c)To compare the Quality of life in the two arms at baseline, 4 months, and 6 months using EORTC QLQ-C30/OV28.
With a power of 80%, 1 sided Type-I error of 0.05 to detect a hazard ratio of 0.7 for median progression-free survival, assuming an mPFS of 3.4 months in the TPC arm and 5.0 months in the OMT arm, and assumed attrition of 2%, we would need 207 events among 276 patients. We, therefore, plan to randomize 280 patients, 140 in each arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- Female
入选标准
- •Histologically confirmed recurrent or metastatic epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer of high-grade serous or endometrioid histology.
- •Patients must have platinum resistant disease (defined as progression within 6 months from completion of a minimum of 4 cycles of platinum containing chemotherapy.
- •Patients must have progressed on or after their most recent line of therapy.
- •Progression must be determined radiographically (RECIST 1.1) and/or CA125 GCIG progression criteria.
- •Participants who had received one line of platinum-based therapy must have received at least four cycles of their initial platinum-containing regimen, had a response (complete or partial), and then had disease progression between 3 and 6 months after their last dose.
- •Patients who have previously received two or three lines of platinum-based therapy must have had disease progression while receiving the therapy or within 6 months after the last dose.
- •Progression will be calculated from the date of the last administered dose of platinum-based therapy to the date of radiographic imaging that shows evidence of progression.
- •Adjuvant± Neoadjuvant and maintenance is considered 1 line of therapy, therapy changed due to toxicity in the absence of progression will be considered part of same line, hormonal therapy will be counted as a separate line unless given in maintenance.
- •Patient must have at least one lesion that meets the definition of measurable disease by RECIST 1.
- •Age 18 years to 85 years
- •ECOG PS 0 to 2
- •Written informed consent 10.
排除标准
- •Patients who have refractory disease (progression during the previous platinum-containing therapy) will be ineligible.
- •Patients with clinical symptoms of bowel obstruction.
- •Surgery within 4 weeks before starting study therapy or anticipated need for major surgery during study treatment.
- •Current or recent treatment with another investigational drug within 30 days before the first study dose.
- •Untreated CNS disease or symptomatic CNS metastasis.
- •Serious concurrent illness or clinically relevant active infections.
- •Patients assigned to PLD stratum only.
- •LVEF below the institutional limit of normal as measured by echocardiography.
- •Pregnant or lactating
- •Patients with clear-cell, mucinous or sarcomatous histology, low grade or borderline disease.
结局指标
主要结局
median progression free survival
时间窗: 3 years
次要结局
- median overall survival(median overall survival)
- overall response rate(after 4 months of intervention)
- quality of life(At 0,4,6 months)
研究者
Raja Pramanik
AIIMS, NEW DELHI