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Vorinostat (SAHA) in Uterine Sarcoma

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ClinicalTrials.gov Identifier: NCT03509207
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : April 26, 2018
Sponsor:
Information provided by (Responsible Party):
Medical University of Graz

Brief 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.


Condition or disease Intervention/treatment Phase
Leiomyosarcoma Endometrial Stromal Tumors Carcinosarcomas Uterine Drug: Vorinostat Oral Capsule Phase 2

Detailed 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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma
Actual Study Start Date : December 14, 2017
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : December 31, 2019


Arm Intervention/treatment
Experimental: Vorinostat, Zolinza Oral Capsules
Vorinostat Oral Capsules 400mg daily
Drug: Vorinostat Oral Capsule
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.
Other Name: Zolinza




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 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)


Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [ Time Frame: 9 months ]
    Evaluated by the amount of clinical adverse experiences



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The investigated condition occurs exclusively in women
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03509207


Contacts
Contact: Martina Dieber-Rotheneder, PhD 0043 316 385 ext 71780 martina.dieber@medunigraz.at
Contact: Edgar Petru, MD 0043 316 385 ext 81082 edgar.petru@medunigraz.at

Locations
Austria
Medical University of Graz, Clinic of Obstetrics and Gynecology Recruiting
Graz, Austria, 8036
Contact: Edgar Petru, Prof. MD    +43 316 385 ext 13810    edgar.petru@medunigraz.at   
Principal Investigator: Edgar Petru, MD         
Sponsors and Collaborators
Medical University of Graz
Investigators
Principal Investigator: Edgar Petru, MD Department of OB/GYN of the Medical University of Graz

Responsible Party: Medical University of Graz
ClinicalTrials.gov Identifier: NCT03509207     History of Changes
Other Study ID Numbers: SAHA
First Posted: April 26, 2018    Key Record Dates
Last Update Posted: April 26, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Medical University of Graz:
Uterine sarcoma
Histone deacetylases

Additional relevant MeSH terms:
Vorinostat
Sarcoma
Leiomyosarcoma
Carcinosarcoma
Mixed Tumor, Mullerian
Endometrial Stromal Tumors
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Muscle Tissue
Neoplasms, Complex and Mixed
Neoplasms, Connective Tissue
Endometrial Neoplasms
Uterine Neoplasms
Uterine Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action