Vorinostat (SAHA) in Uterine Sarcoma

NCT03509207 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: SAHA
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Leiomyosarcoma; Endometrial Stromal Tumors; Carcinosarcomas Uterine

Keywords

Uterine sarcoma; Histone deacetylases

Outcome Measures

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)

  9 months

Secondary Outcomes (1)

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

  9 months

Study Arms (1)

Vorinostat, Zolinza Oral Capsules

EXPERIMENTAL

Vorinostat Oral Capsules 400mg daily

Drug: Vorinostat Oral Capsule

Interventions

Vorinostat Oral Capsule DRUG

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

Vorinostat, Zolinza Oral Capsules

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The investigated condition occurs exclusively in women
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz, Clinic of Obstetrics and Gynecology

Graz, 8036, Austria

Location

MeSH Terms

Conditions

Leiomyosarcoma; Endometrial Stromal Tumors

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neoplasms, Connective Tissue; Endometrial Neoplasms; Uterine Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Prof. Edgar Petru
• Organization: Medical University of Graz

edgar.petru@medunigraz.at

0043 31638581082

Study Officials

• Edgar Petru, MD

  Department of OB/GYN of the Medical University of Graz

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 26, 2018
• Study Start: December 14, 2017
• Primary Completion: February 4, 2019
• Study Completion: February 4, 2019
• Last Updated: August 4, 2020
• Results First Posted: July 27, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)