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TerminatedNCT03509207Updated Aug 4, 2020Results posted

Vorinostat (SAHA) in Uterine Sarcoma

A Phase 2 interventional study of Vorinostat Oral Capsule in Leiomyosarcoma, Endometrial Stromal Tumors and Carcinosarcomas Uterine, sponsored by Medical University of Graz. Terminated at 1 site in Austria. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-08-04.

Sponsored by Medical University of Graz · Phase 2, Interventional, and Treatment

Why this study was terminated
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
Phase
Phase 2
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years and older
Sex
Female
01

Study 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.

Read the 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).

02

Conditions studied

  • Leiomyosarcoma
  • Endometrial Stromal Tumors
  • Carcinosarcomas Uterine

Keywords

  • Uterine sarcoma
  • Histone deacetylases
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study arms

  • Experimental
    Vorinostat, Zolinza Oral Capsules

    Vorinostat Oral Capsules 400mg daily

    Drug: Vorinostat Oral Capsule

Interventions

  • DrugVorinostat 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.

    Also known as: Zolinza

05

What researchers measure

Primary outcomes

  1. 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)

    Time frame: 9 months

Secondary outcomes

  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

    This endpoint is evaluated by the amount of clinical adverse experiences.

    Time frame: 9 months

06

Results

Posted Jul 27, 2020

Participant flow

3 patients were enrolled. The study was prematurely closed due to the sluggish patient recruitment and the difficult acquisition of the investigational product.

Participant flow — Overall Study
MilestoneVorinostat, Zolinza Oral Capsules
Started3
Completed1
Not completed2
Withdrew: Death2

Outcome measures

PrimaryProgression-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)

Time frame:
9 months

No measurements were reported for this outcome.

SecondaryIncidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

This endpoint is evaluated by the amount of clinical adverse experiences.

Time frame:
9 months

No measurements were reported for this outcome.

Adverse events

Collected over From enrolment to study completion per Patient, up to 41 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Vorinostat, Zolinza Oral Capsules2/3 (66.7%)2/3 (66.7%)0/3 (0%)
Most frequent serious events
Most frequent serious events
EventVorinostat, Zolinza Oral Capsules
Death of uterine carcinomaReproductive system and breast disorders2/3
pleural effusionRespiratory, thoracic and mediastinal disorders2/3
abscess of the vaginal vaultReproductive system and breast disorders1/3

Baseline characteristics

Statistical evaluation was not possible as only 1 Patient reached end point 1.

Age, Categorical
Age, Categorical(Participants)Vorinostat, Zolinza Oral Capsules
<=18 years0
Between 18 and 65 years3
>=65 years0
Sex: Female, Male
Sex: Female, Male(Participants)Vorinostat, Zolinza Oral Capsules
Female3
Male0
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Vorinostat, Zolinza Oral Capsules
Region of Enrollment
Region of Enrollment(participants)Vorinostat, Zolinza Oral Capsules
Austria3
07

Study locations

1 site
  • Medical University of Graz, Clinic of Obstetrics and Gynecology
    Graz, 8036, Austria
08

References and documents

Study documents

  • Study protocol · Dec 22, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03509207
Lead sponsor
Medical University of Graz
Responsible party
Sponsor
First posted
Apr 26, 2018
Start date
Dec 14, 2017
Primary completion
Feb 4, 2019
Completion
Feb 4, 2019
Results posted
Jul 27, 2020
Last update
Aug 4, 2020

Study contacts

Edgar Petru, MD
principal investigator · Department of OB/GYN of the Medical University of Graz

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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