07-742 Phase I/ Feasibility Study of Short Term Fondaparinux (Arixtra) in Chemotherapy-Pretreated Ovarian Carcinoma Patients at High Risk of Progression
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).
研究概览
简要总结
The purpose of this study is to assess feasibility and safety of using once daily Fondaparinux Sodium (ARIXTRA®) in patients with ovarian cancer who are in 'clinical remission' (no clinical evidence of disease) after chemotherapy but at high risk of ovarian cancer recurrence.
详细描述
Rationale:
A large body of work supports the association of abnormal coagulation (blood clot formation) and malignancy. A coagulation enzyme thrombin is able to 1) enhance cancer cell adhesion to platelets and endothelial cells 2) stimulate tumor cell growth, 3) increase metastasis and 4) stimulate tumor angiogenesis.
Thrombin inhibition has anti-metastatic and anti-tumor activity in mouse models. Recent meta-analysis of 4 major randomized clinical trials that have evaluated the effect of anticoagulants on overall survival in cancer patients comparing low molecular weight heparin (LMWH) to placebo demonstrates a 13% risk reduction in mortality at 1 year and 10% risk reduction at 2 years, which is statistically significant and independent of the potential confounding effect of anticoagulation in the prevention of venous thromboembolic disease.
Fondaparinux sodium (ARIXTRA® ) is a highly effective newer anticoagulant that is a fully synthetic pentasaccharide. Arixtra binds to antithrombin III and subsequently inhibits Factor Xa and hence thrombin generation. Arixtra has an excellent safety profile in clinical trials of over 10,000 patients. When compared to LMWHs, ARIXTRA® has a potential pharmacokinetic advantage based on its longer half-life of 16-17 hours.
Hypothesis:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients 18 years of age and ≤75 years of age
- •Biopsy-proven ovarian, tubal or primary peritoneal epithelial adenocarcinomas;
- •Performance status 0,1 (ECOG) ( table 2)
- •Patients at high risk of clinical relapse: first remission stage III/IV who were suboptimally debulked (residual disease >1 cm)
- •Patients of any stage who have recurred and are in second chemotherapy induced remission. Clinical remission defined as:
- •absence of symptoms that may be related to disease
- •imaging without abnormalities greater then or equal to 1 cm suspicious for disease (no ascites)
- •CA 125 obtained x 1 and <35 units/ml.
- •Adequate end organ function, defined as the following:
- •Total bilirubin < 1.5 x ULN
- •SGOT and SGPT < 2.5 x UNL
- •Creatinine < 1.5 x ULN
- •ANC > 1.5 x 109/L
- •Platelets > 100 x 109/L
- •Weight ≥ 50 kg
排除标准
- •Patients with performance status ECOG =2,3,4
- •Patients who are on warfarin or prior therapeutic anticoagulation
- •Patient has another primary malignancy that has required active intervention within 5 years, with the exception of basal cell skin cancer or a cervical carcinoma in situ.
- •Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection).
- •Patient who had a major surgery within 2 weeks prior to study entry
- •Patients with the following lab abnormalities:
- •WBC <3000
- •absolute neutrophil count < 1,500
- •hemoglobin <10 g/dL
- •platelet < 100,000
- •creatinine clearance <30 cc/min
- •serum ALT, AST, or total bilirubin >1.5X the upper limit of normal
- •Patients with known bleeding disorder
结局指标
主要结局
Estimate the proportion of patients who complete an eight week course of once daily administration of fondaparinux (Arixtra).
时间窗: 15 months
次要结局
- Time to Recurrence(24 months)