Phase IB Study of Lenalidomide (Revlimid®) With Liposomal Doxorubicin (Doxil®) and Bevacizumab (Avastin®) for Patients With Platinum Resistant Ovarian Cancer.
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.
研究概览
简要总结
This study will test the feasibility of combining 3 drugs, Revlimid with Doxil and Bevacizumab,and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.
详细描述
The combination of Doxil with Avastin has several aspects of interest to ovarian cancer treatment: 1) independent single-agent activity, 2) enhanced localization of Doxil is possible tumoral interstitial pressure via increased half-life (if liposomal egress is diminished) and decreased [42], 3) improved Doxil distribution, and 4) likely favorable toxicity profile since Doxil's only common problematic toxicity is to the skin (palmar-plantar erythrodysesthesia or PPE). Lenalidomide has also antiangiogenic properties, with a different mechanism of action than Avastin. Given the preliminary results of the effect of the combination of Doxil with Avastin, showing an increase in progression-free survival, we are interested in using a new thalidomide analog to maximize the angiogenic inhibition. This study will test the feasibility of combining all 3 drugs, and gather preliminary data on the potential activity of the combination in patients with platinum resistant/refractory ovarian cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •EOC patients must be platinum resistant/refractory (see 1.1 for definition) and be considered by the attending physician capable of being treated in this study according to GCP.
- •Measurable disease by RECIST criteria or evaluable disease by GCIC criteria
- •No prior anthracycline or lenalidomide use, unless the dose received was equal or less than one cycle and the patient did not progress on treatment.
- •Subjects must have calculated creatinine clearance > 60ml/min by Cockcroft-Gault formula during the escalation phase.
- •Subjects must have calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula during the expansion phase. See section below, "Dosing Regimen", regarding lenalidomide dose adjustment for calculated creatinine clearance > 30ml/min and < 60ml/min.
- •Understand and voluntarily sign an informed consent form.
- •All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
- •Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
- •No contraindication to anticoagulation
排除标准
- •Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking lenalidomide).
- •Concurrent use of other anti-cancer agents or treatments.
- •Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
- •History of thromboembolic event within the last 3 months
- •Known hypersensitivity to any component of Avastin
研究组 & 干预措施
Arm 1
At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.
干预措施: Lenalidomide, Liposomal Doxorubicin, Bevacizumab (Drug)
Arm 1
At the expansion phase: Revlimid 20 mg (days 1-21), Doxil 30 mg/m2 on Day 1 and Avastin 15 mg/kg on Day 1, every 3 weeks. If this regimen is not cumulatively tolerable, Avastin will be administered every other course. Patients will be received up to 6 cycles or disease progression, followed by Revlimid maintenance at 25 mg PO q Day for 3 weeks every 4 weeks in patients with stable disease.
干预措施: Revlimid, Doxil, Avastin (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) of the 3 drug combination and recommend a dose for phase II studies.
时间窗: 6-8 months
次要结局
- Progression-free survival (PFS) after treatment with Revlimid plus Avastin and Doxil.(6-8 Months)
- Acute and subacute toxicities of Lenalidomide plus Doxil and Avastin for the treatment of ovarian cancer.(6-8 Months)