Study on Efficacy and Tolerability of Vorinostat in Patients With Advanced, Metastatic Soft Tissue Sarcoma (STS)

Soft Tissue Sarcoma Clinical Trial

— SAHA-I  

Official title:

A Phase II Study to Investigate the Efficacy and Tolerability of Vorinostat in Patients Suffering From Advanced, Metastatic Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00918489
• Other study ID #: SAHA-I
• Status: Completed
• Phase: Phase 2
• Start date: May 2010
• Est. completion date: September 2013

Study information

• Verified date: October 2018
• Source: Heidelberg University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary objective of the study is to investigate the efficacy of vorinostat in patients suffering from selected histological types of soft tissue sarcoma. Further evaluations relate to the safety and tolerability of vorinostat, its pharmacokinetics (course of plasma concentration over time) and pharmacodynamics (mode of action). Only subjects with advanced, metastatic disease will be included in this trail.

Description:

The treatment with vorinostat will be administered daily over 28 days. This period will be referred to as a therapy cycle. Two consecutive therapy cycles will be separated by a 7-days therapy break. In case of a good response and no relevant side effects, the treatment with vorinostat can be continued for up to 1 year after begin of the treatment. If any relevant side effects or intolerability occur, the dose and/or schedule of administration will be modified according to the pre-defined criteria.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients with verified, metastatic soft tissue sarcoma of the following histologies:

• undifferentiated highgrade pleomorphic sarcoma/pleomorphic malignant fibrous histiocytoma,

• undifferentiated pleomorphic sarcoma with grand cells/grand cell fibrotic histiocytoma,

• undifferentiated pleomorphic sarcoma with prominent inflammation/inflamed MFH,

• myxofibrosarcoma,

• liposarcoma,

• synovial sarcoma,

• rhabdomyosarcoma (pleomorph, alveolar und embryonal),

• leiomyosarcoma,

• adult fibrosarcoma,

• angiosarcoma,

• malignant hemangiopericytoma/ malignant solitaire fibrous tumor,

• malignant peripheral neurilemma tumor,

• extraskeletal mesenchymal chondrosarcoma,

• extraskeletal myxoid chondrosarcoma,

• undifferentiated sarcoma of non other specified (NOS) type.

2. Verified relapse or disease progression at study inclusion, i.e. therapeutic failure of the first line therapy with anthracyclines,

3. Measurable disease according to the RECIST criteria,

4. Previous systemic therapy of advanced and/or metastatic disease,

5. An interval of at least 4 weeks since the last surgery, chemotherapy or radiation,

6. Age over 18,

7. Following laboratory findings:

• ANC = 1.0 x 10³/mm³,

• platelets = 100.000/mm³,

• hemoglobin = 9 g/dl,

• creatinin < 1.5 x ULN (upper limit of normal),

• AST and ALT < 2.5 x ULN,

• total bilirubin < 1.5 x ULN,

8. Life expectancy of at least 12 weeks,

9. Negative pregnancy test,

10. Consent for an effective contraception during and up to 6 month after the study completion.

11. Written informed consent,

12. Ability to understand the goal and the consequences of this trial.

Exclusion Criteria:

1. Proof of the following histologies:

• gastrointestinal stromal tumor (GIST),

• malignant mesothelioma,

• neuroblastoma,

• osteosarcoma,

• Ewing's sarcoma/PNET,

2. Concurrent radio- or chemotherapy,

3. Participation in another interventional trial within 4 weeks prior to the inclusion,

4. Previous therapy with another HDAC-inhibitor (e.g. depsipeptide, MS-275, LAQ-824, PXD-101 und valproic acid). Patients, who underwent a therapy with valproic acid for treatment of seizures, can be included after a wash-out period of at least 30 days,

5. Symptomatic brain metastases, that have not been treated by radiotherapy. The interval between the last radiation and the study inclusion must not be shorter than 30 days,

6. Previous malignant disease (except for a non-melanoma of the skin and a carcinoma in situ of uterus), unless in complete remission and after the last therapy for at least 5 years,

7. Ejection fraction < 40 %,

8. Nursing,

9. Known allergy against the IMP or drugs with similar chemical structure or additives,

10. Active hepatitis B and/or C and HIV-infection

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• Vorinostat
Daily administration of 400mg vorinostat on 28 days (one therapy cycle). Seven days of therapy break between two consecutive cycles.

Locations

Country	Name	City	State
Germany	Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf	Düsseldorf	Nordrhein-Westfalen
Germany	Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover	Hannover	Niedersachen
Germany	Comprehensive Cancer Center North, University Hospital Kiel	Kiel
Germany	Sarcoma Center Mannheim, University Hospital Mannheim	Mannheim
Germany	Center for Soft Tissue Sarcoma, University Hospital Tübingen	Tübingen
Germany	Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen	Tübingen	Baden-Württemberg
Germany	Comprehensive Cancer Center Ulm (CCCU)	Ulm

Sponsors (2)

Lead Sponsor	Collaborator
Heidelberg University	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of the efficacy of vorinostat on the basis of progression free survival (PFS) up to 1 year after first administration of the IMP.		Up to 1 year
Secondary	Evaluation of the efficacy of vorinostat on the basis of overall survival up to 1 year after first administration of the IMP. Investigation on pharmacokinetics und pharmacodynamics of vorinostat. Evaluation of safety and tolerability of vorinostat.		Up to 1 year