Vorinostat (SAHA) in Uterine Sarcoma

• Status: Terminated
• Trial end date: 2019-02-04
• Target enrollment: 0
• Participant gender: Female

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical University of Graz
• Treatments: Vorinostat

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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