Vorinostat (SAHA) in Uterine Sarcoma
Condition: Leiomyosarcoma; Endometrial Stromal Tumors; Carcinosarcomas Uterine
MeSH terms: Sarcoma; Leiomyosarcoma; Carcinosarcoma; Mixed Tumor, Mullerian; Endometrial Stromal Tumors
Intervention: Vorinostat Oral Capsule
Intervention description: Vorinostat, 400 mg orally once daily for the first 14 days of a 21 day cycle Treatment will be continued for 4 cycles. Patients with a response or stable disease after 4 cycles 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 period of 9 months.
Intervention MeSH terms: Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Uterine sarcoma; Histone deacetylases

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.
    

Eligibility 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