A Randomized Phase II Study of Paclitaxel/Carboplatin With or Without Sorafenib in the First-Line Treatment of Patients With Stage III/IV Epithelial Ovarian Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 17
- 主要终点
- 2-year Progression-free Survival
研究概览
简要总结
This trial will compare the efficacy and toxicity of standard first-line chemotherapy alone vs. standard chemotherapy plus sorafenib in patients with stage III/IV ovarian cancer following cytoreductive surgery. Patients with residual large volume disease and/or bowel involvement will be excluded, to minimize the risk of bowel perforation.
详细描述
All patients must be at least 4 weeks from cytoreductive surgery before starting treatment. Patients will be randomized to receive treatment with either paclitaxel/carboplatin + sorafenib or paclitaxel/carboplatin. Paclitaxel/carboplatin will be repeated every 21 days for a maximum of 6 cycles. Patients with objective response/stable disease after completing 6 courses of chemotherapy will continue sorafenib until disease progression or for a total of 12 months.
- Regimen A:
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1
Carboplatin AUC 6 infused over 20 minutes IV, Day 1
Sorafenib 400mg PO bid
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed, stage III or IV epithelial ovarian carcinoma
- •No previous treatment with chemotherapy or radiation therapy
- •All patients must have undergone cytoreductive surgery, with the
- •following results:
- •No residual tumor nodule > 3cm
- •No residual tumor involvement of the bowel (ie. invasion into bowel
- •No residual intestinal obstruction
- •Measurable or evaluable disease. Patients with elevated CA-125 levels
- •and/or evaluable disease per RECIST criteria are eligible.
- •ECOG performance status 0 or
- •ANC ≥ 1500/µL, platelets ≥ 100,000/µL, hemoglobin ≥ 9.0 g/dL.
- •Total bilirubin ≤ 1.5 x upper limits of normal (ULN), ALT and AST ≤ 2.5 x
- •ULN (≤ 5 x ULN for patients with liver metastases)
- •Serum creatinine _ 1.5 x ULN
- •INR < 1.5 or a PT/PTT within normal limits. Patients receiving anticoagulation
- •treatment with an agent such as warfarin or heparin may be
- •allowed to participate. For patients on warfarin, the INR may be > 1.5,
- •and should be measured prior to initiation of sorafenib and monitored at
- •least weekly until INR is stable in the desired therapeutic range.
- •Women of childbearing potential must have a negative serum pregnancy
- •test performed within 7 days prior to start of treatment.
- •Patients must be able to understand the nature of this study and give
- •written informed consent.
排除标准
- •Age < 18 years
- •Active cardiac disease, including: A) congestive heart failure > class II
- •NYHA , B) unstable angina or onset of angina within last 3 months, C) myocardial infarction within 6 months
- •Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- •Patients with CNS metastases. Patients with neurological symptoms
- •must undergo a CT scan/MRI of the brain to exclude brain metastasis.
- •Uncontrolled hypertension defined as systolic blood pressure > 150mmHg or diastolic pressure > 90mmHg, despite optimal medical management
- •Known HIV, chronic hepatitis B or chronic hepatitis C infections
- •Women who are pregnant or lactating. Women of childbearing potential
- •must agree to use adequate contraception from time of study entry until
- •at least 3 months after the last administration of study drug.
- •Active clinically serious infection (> grade 2)
- •Thrombotic or embolic events such as cerebral vascular accident
- •including transient ischemic attacks within the last 6 months.
- •Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of
- •starting treatment.
- •Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of
- •starting treatment
- •Serious non-healing wound, ulcer, or bone fracture
- •Evidence of history of bleeding diathesis or coagulopathy
- •Major surgery, open biopsy, or significant traumatic injury within 4 weeks
- •of starting treatment.
- •Any condition that impairs the ability to swallow whole pills
- •Patients with any type of malabsorption
- •Known or suspected allergy to any of the agents used in this treatment
- •Use of St. John's Wort or rifampin
研究组 & 干预措施
Paclitaxel/Carboplatin/Sorafenib
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
干预措施: Sorafenib (Drug)
Paclitaxel/Carboplatin/Sorafenib
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
干预措施: Paclitaxel (Drug)
Paclitaxel/Carboplatin/Sorafenib
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV, Day 1 Sorafenib 400mg PO bid
干预措施: Carboplatin (Drug)
Paclitaxel/carboplatin
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV
干预措施: Paclitaxel (Drug)
Paclitaxel/carboplatin
Paclitaxel 175 mg/m2 1-3 hour IV infusion, Day 1 Carboplatin AUC 6 infused over 20 minutes IV
干预措施: Carboplatin (Drug)
结局指标
主要结局
2-year Progression-free Survival
时间窗: 2 years
The proportion of patients with progression-free survival at 2 years. Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
次要结局
- Overall Survival (OS)(18 months)
- Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib(18 months)
- Overall Response Rate (ORR)(18 months)