Overview

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