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Vorinostat (SAHA) in Uterine Sarcoma

Primary Purpose

Leiomyosarcoma, Endometrial Stromal Tumors, Carcinosarcomas Uterine

Status
Terminated
Phase
Phase 2
Locations
Austria
Study Type
Interventional
Intervention
Vorinostat Oral Capsule
Sponsored by
Medical University of Graz
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leiomyosarcoma focused on measuring Uterine sarcoma, Histone deacetylases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept 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

Sites / Locations

  • Medical University of Graz, Clinic of Obstetrics and Gynecology

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vorinostat, Zolinza Oral Capsules

Arm Description

Vorinostat Oral Capsules 400mg daily

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
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

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
This endpoint is evaluated by the amount of clinical adverse experiences.

Full Information

First Posted
March 27, 2018
Last Updated
July 27, 2020
Sponsor
Medical University of Graz
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1. Study Identification

Unique Protocol Identification Number
NCT03509207
Brief Title
Vorinostat (SAHA) in Uterine Sarcoma
Official Title
A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
The early termination was NOT due to safety reasons, terminated because of the very slow recruitment and problematic access to the study medication in Europe
Study Start Date
December 14, 2017 (Actual)
Primary Completion Date
February 4, 2019 (Actual)
Study Completion Date
February 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University of Graz

4. Oversight

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

5. Study Description

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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leiomyosarcoma, Endometrial Stromal Tumors, Carcinosarcomas Uterine
Keywords
Uterine sarcoma, Histone deacetylases

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Vorinostat, Zolinza Oral Capsules
Arm Type
Experimental
Arm Description
Vorinostat Oral Capsules 400mg daily
Intervention Type
Drug
Intervention Name(s)
Vorinostat Oral Capsule
Other Intervention Name(s)
Zolinza
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.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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)
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Description
This endpoint is evaluated by the amount of clinical adverse experiences.
Time Frame
9 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
The investigated condition occurs exclusively in women
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edgar Petru, MD
Organizational Affiliation
Department of OB/GYN of the Medical University of Graz
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of Graz, Clinic of Obstetrics and Gynecology
City
Graz
ZIP/Postal Code
8036
Country
Austria

12. IPD Sharing Statement

Plan to Share IPD
No

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Vorinostat (SAHA) in Uterine Sarcoma

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