LeiomyosarcomaPhase 2NCT03509207
Vorinostat (SAHA) in Uterine Sarcoma
A Phase 2 study testing Vorinostat Oral Capsule in people with Leiomyosarcoma and Endometrial Stromal Tumors, run by Medical University of Graz at 1 site in Austria.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Leiomyosarcoma, Endometrial Stromal Tumors, Carcinosarcomas Uterine
- What is being tested?
- Vorinostat Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteAustria
- Study dates
- 14 Dec 2017to 4 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Austria1 site
Medical University of Graz, Clinic of Obstetrics and Gynecology
Graz, 8036
About this study
Official title: A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma
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).
- Being tested
- Vorinostat Oral Capsule
- Keywords
- Uterine sarcoma, Histone deacetylases
- Medical subject headings
- Leiomyosarcoma, Endometrial Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat Oral CapsuleDrug
Also called Zolinza
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.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat, Zolinza Oral Capsules | Experimental | Vorinostat Oral Capsules 400mg daily Receives: Drug: Vorinostat Oral Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2018
- Study start14 Dec 2017
- Primary completion4 Feb 2019
- Study completion4 Feb 2019
Why it 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
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for LeiomyosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Graz
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edgar Petru, MD, Principal investigator, Department of OB/GYN of the Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03509207
- Sponsor's protocol ID
- SAHA
- Status last verified
- Jul 2020
- First submitted
- 27 Mar 2018
- Last updated
- 4 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Peroral Vorinostat (SAHA) in Patients With Refractory Histone Deacetylase-positive Uterine Sarcoma
- ClinicalTrials.gov ID
- NCT03509207
- Acronym / sponsor ID
- SAHA
- Keywords
- Uterine sarcoma, Histone deacetylases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Medical University of GrazUniversity, hospital or other
- Study start
- 14 Dec 2017 (actual)
- Primary completion
- 4 Feb 2019 (actual)
- Study completion
- 4 Feb 2019 (actual)
- First posted
- 26 Apr 2018 (actual)
- Results
- Posted 27 Jul 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vorinostat, Zolinza Oral Capsules | Experimental | Drug: Vorinostat Oral CapsuleVorinostat Oral Capsules 400mg daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed metastatic uterine sarcoma (endometrial stromal sarcoma, undifferentiated uterine sarcoma, leiomyosarcoma, adenosarcoma and carcinosarcoma
Key exclusion criteria (18 listed)
- Lack of or low expression of HDAC (see 4.1 "Pre-Screening")
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vorinostat Oral CapsuleAlso: ZolinzaVorinostat, 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. | Drug | Vorinostat, Zolinza Oral Capsules |
Primary outcome
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)
1 secondary outcome
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: 9 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edgar Petru, MD principal investigator
Department of OB/GYN of the Medical University of Graz
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vorinostat Oral Capsule in people with Leiomyosarcoma and Endometrial Stromal Tumors, run by Medical University of Graz at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 4 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) (time frame: 9 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2020.