A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Uterine sarcomas are rare tumors with a poor prognosis.
The main purpose of this phase II proof-of-principle- pilot study is to test the efficacy of the hydroxamic acid-based Histone deacetylase inhibitor (HDACI) Vorinostat (SAHA) as monotherapy in patients with HDAC-positive, progressive, metastatic uterine sarcomas and mixed epithelial and mesenchymal tumors after prior anti-proliferative therapy.
详细描述
This is an open-label, single arm, proof of concept-study of the HDAC-inhibitor vorinostat in patients with refractory uterine sarcoma that have been pre-tested for an high expression of HDAC. Patients will receive Vorinostat, 400 mg (4 capsules á 100mg of Zolinza) orally once daily for the first 14 days of a 21 day cycle. Treatment will be continued for 4 cycles (treatment period 1). Patients with a response or stable disease after 4 cycles as determined by computed tomography (CT) of target an non target-lesions will be continued on vorinostat therapy at the tolerated schedule and dosage until disease progression, unacceptable toxicity or patients' withdrawal of the consent. At the maximum, a total of 12 cycles will be administered over a 9 months period (treatment periods 2 and 3).
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed metastatic uterine sarcoma (endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyosarcoma, adenosarcoma and carcinosarcoma
- •High HDAC-positivity of the tumor determined by immunohistochemistry
- •Patients must have received prior systemic antineoplastic therapy
- •Patient is not amenable for curative therapy
- •Age >= 18 years
- •Estimated life expectancy > 3 months
- •Measurable disease on CT/MRI (at least one measurable lesion >1cm) or chest X-ray (at least one measurable lesion >2cm)
- •Karnofsky performance status of 60-100
- •Adequate hematologic, renal and hepatic function
- •Subject is able to swallow and retain oral medication and does not have uncontrolled emesis
- •No fertility preserved
- •Written informed consent
排除标准
- •Lack of or low expression of HDAC (see 4.1 "Pre-Screening")
- •Significant cardiac disease
- •Other invasive malignant tumor diagnosed within the last 5 years (e.g. metastases from breast cancer in the last 3 years)
- •Significant bowel obstruction
- •Severe uncontrolled infection
- •Known HIV-positivity
- •Symptomatic brain metastasis or leptomeningeal disease
- •Pre-existing significant liver disease, severe hepatic impairment (Bilirubin no greater than 1.5 times upper limit of normal (ULN) and/or aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) greater than 2.5 times ULN)
- •Known history of allergic reaction to vorinostat or similar medications
- •Systemic therapy or an investigational agent within 21 days prior to study inclusion
- •Uncontrolled hypertension (sustained systolic blood pressure > 150 mmHg or diastolic pressure > 100 mmHg despite optimal medical management)
- •Major surgery within 3 weeks of enrollment when diagnosed at an early stage
- •Symptomatic congestive heart failure
- •Unstable angina pectoris or cardiac arrhythmia
- •Myocardial infarction within last 6 months
- •Known active hepatitis B or hepatitis C
- •Psychiatric illness/social situations that would limit compliance with study requirements-
- •Prior history of thrombotic or thromboembolic events, unless adequately controlled by anticoagulant therapy
研究组 & 干预措施
Vorinostat, Zolinza Oral Capsules
Vorinostat Oral Capsules 400mg daily
干预措施: Vorinostat Oral Capsule (Drug)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: 9 months
Change from Baseline Tumor Size to last available observation with respect to progress as defined by RECIST 1.1 (CT-Scan every 12 weeks up to 9 months)
次要结局
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(9 months)