Single-arm, Multicenter, Open Label Phase II Trial to Evaluate the Efficacy of Pazopanib in Combination With Paclitaxel in Advanced and Relapsed Angiosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 10
- 主要终点
- Rate of Progression-free Survival
研究概览
简要总结
Open-label phase II trial investigating the efficacy and safety of the investigational combination of pazopanib and paclitaxel.
详细描述
Open-label phase II trial investigating the efficacy and safety of the investigational combination of pazopanib and paclitaxel.This multi-center, open-label, prospective, single arm phase II study was designed to evaluate the clinical efficacy and safety of the experimental combination of pazopanib with paclitaxel in the treatment of patients with advanced or metastatic angiosarcoma.The safety evaluations (physical examination, laboratory checks as defined in protocol, toxicity/adverse event assessment according Eastern Cooperative Oncology Group version 4.0) are scheduled every cycle at day 1, 8, 15 and 29 (= day 1 of the next cycle).
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
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must provide written informed consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow-up. Note: Procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging studies) and obtained prior to signing informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol.
- •Age ≥ 18 years
- •Life expectancy > 3 months
- •Ability to swallow tablets
- •Histological confirmed angiosarcoma, primary and secondary angiosarcoma (e.g. radiation-induced or angiosarcoma in chronical lymphedema) are eligible.
- •Tumor must be locally advanced (unresectable) or metastatic. A progression must be documented within a 6-month period prior to screening.
- •Eastern Cooperative Oncology Group performance status ≤ 2
- •At least one measurable skin lesion or one measurable radiological (CT or MRI) target lesion (RECIST 1.1)
- •Adequate organ system function as described in protocol
- •A female is eligible to enter and participate in this study if she is either of non childbearing potential (defined in protocol) or childbearing potential with negative pregnancy test within 2 weeks prior to the first dose of study drug and agrees to use adequate contraception (as defined in protocol) during the study and for 30 days after the last dose of study drug.
- •All sexually active male patients must agree to use adequate methods of birth control (see protocol) throughout the study and for 30 days after the last dose of study drug.
排除标准
- •Patients who need an active treatment for another malignant disease other than angiosarcoma
- •Prior treatment with taxane within the last 12 months before study entry
- •History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal sarcomatosis.(see protocol)
- •Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding (see protocol)
- •Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product (see protocol)
- •Presence of uncontrolled infection
- •QT prolongation interval (QTc) > 480 msec.
- •Clinically significant cardiovascular disorders within the past 6 months
- •Major surgery or trauma within 28 days prior to first dose of investigational product and/or presence of any non-healing wound, fracture, or ulcer
- •Poorly controlled hypertension (see protocol)
- •Evidence of active bleeding or bleeding diathesis
- •Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- •Uncontrolled seizures, disorders of the CNS or psychiatric disorders which may put patient safety at risk, prevent giving informed consent or impact the patient's compliance with the use of study medication
- •Women who are pregnant or breast feeding
- •Patients who are not able or not willing to interrupt the intake of medications that are not allowed according to study protocol for at least 14 days before start of study medication and for the whole study period
- •Chemotherapy or radiotherapy within 14 days before start of study medication
- •Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia
研究组 & 干预措施
Pazopanib + Paclitaxel
Paclitaxel administered every 28 days at day 1, day 8 and day 15 as a 2h intravenous infusion in a dose of 70mg/m2 in combination with pazopanib in a daily oral dose of 800mg (2x400mg)
干预措施: Pazopanib + Paclitaxel (Drug)
结局指标
主要结局
Rate of Progression-free Survival
时间窗: 6 Month
The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
Rate of Progression-free Survival, Subgroup 2 Analysis
时间窗: 6 months
Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into primary angiosarcoma versus secondary angiosarcoma. The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
Rate of Progression-free Survival, Subgroup 1 Analysis
时间窗: 6 months
Rate of progression-free survival for Subgroup 1 categorizing the 12 participants who showed PFS after 6 months into cutaneous angiosarcoma versus visceral angiosarcoma The diagnosis of progession is based on tumor measurements assessed 182 days +/- 32 days after start of treatment (with imaging date as reference date) and according to the RECIST Version 1.1 criteria based on a predefined set of target lesions and non-target lesions.
次要结局
- Adverse Events and Serious Adverse Events(30 days after EOS of last patient or end of overall study observation period (22 months))
- Overall Survival, Subgroup 1 Analysis(from start of treatment until death within study's actual observation time for OS (22 months))
- Response Rate (RR)(determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR)
- Response Rate (RR), Subgroup 2 Analysis(determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR)
- Overall Survival(from start of treatment until death within study's actual observation time for OS (22 months).)
- Overall Survival, Subgroup 2 Analysis(from start of treatment until death within study's actual observation time for OS (22 months))
- Response Rate (RR), Subgroup1 Analysis(determined every 8 weeks during first 6 month then every 12 weeks in follow-up period until progression or death or end of overall study observation period (22 months), then evaluated as BOR)
研究者
Peter Hohenberger
Prof. Dr. med.
Universitätsmedizin Mannheim