Vorinostat (SAHA) in Uterine Sarcoma

Medical University of Graz

Status and phase

Terminated

Phase 2

Conditions

Carcinosarcomas Uterine

Leiomyosarcoma

Endometrial Stromal Tumors

Treatments

Drug: Vorinostat Oral Capsule

Study type

Interventional

Funder types

Other

Identifiers

NCT03509207

SAHA

Details and patient eligibility

About

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.

Full description

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).

Enrollment

3 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

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