Study on Efficacy and Tolerability of Vorinostat in Patients With Advanced, Metastatic STS - Full Text View

Sponsor:	University of Heidelberg
Collaborator:	Merck
Information provided by:	University of Heidelberg
ClinicalTrials.gov Identifier:	NCT00918489

Purpose

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.

Condition	Intervention	Phase
Soft Tissue Sarcoma	Drug: Vorinostat	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study to Investigate the Efficacy and Tolerability of Vorinostat in Patients Suffering From Advanced, Metastatic Soft Tissue Sarcoma

Resource links provided by NLM:

MedlinePlus related topics: Soft Tissue Sarcoma

Drug Information available for: Suberoylanilide hydroxamic acid

U.S. FDA Resources

Further study details as provided by University of Heidelberg:

Primary Outcome Measures:

Evaluation of the efficacy of vorinostat on the basis of progression free survival (PFS) up to 1 year after first administration of the IMP. [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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. [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:

40

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

Detailed 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
Verified relapse or disease progression at study inclusion, i.e. therapeutic failure of the first line therapy with anthracyclines,
Measurable disease according to the RECIST criteria,
Previous systemic therapy of advanced and/or metastatic disease,
An interval of at least 4 weeks since the last surgery, chemotherapy or radiation,
Age over 18,
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,
Life expectancy of at least 12 weeks,
Negative pregnancy test,
Consent for an effective contraception during and up to 6 month after the study completion.
Written informed consent,
Ability to understand the goal and the consequences of this trial.

Exclusion Criteria:

Proof of the following histologies:
- gastrointestinal stromal tumor (GIST),
- malignant mesothelioma,
- neuroblastoma,
- osteosarcoma,
- Ewing's sarcoma/PNET,
Concurrent radio- or chemotherapy,
Participation in another interventional trial within 4 weeks prior to the inclusion,
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,
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,
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,
Ejection fraction < 40 %,
Nursing,
Known allergy against the IMP or drugs with similar chemical structure or additives,
Active hepatitis B and/or C and HIV-infection

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00918489

Contacts

Contact: Gerlinde Egerer, MD	+49 06221 56 ext 8002	Gerlinde.Egerer@med.uni-heidelberg.de
Contact: Thomas Schmitt, MD	+49 06221 56 ext 39067	Thomas.Schmitt@med.uni-heidelberg.de

Locations

Germany, Baden-Württemberg
Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen
Tübingen, Baden-Württemberg, Germany, D-72076
Germany, Niedersachen
Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover
Hannover, Niedersachen, Germany, D-30625
Germany, Nordrhein-Westfalen
Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf
Düsseldorf, Nordrhein-Westfalen, Germany, D-40479

Sponsors and Collaborators

University of Heidelberg

Merck

Investigators

Study Director:

Gerlinde Egerer, MD

Department of Internal Medicine V, Universtity Hospital Heidelberg

More Information

No publications provided

Responsible Party:	Department of Internal Medicine V, University Hospital Heidelberg ( Coordinating investigator: PD Dr. Gerlinde Egerer )
Study ID Numbers:	SAHA-I
Study First Received:	June 10, 2009
Last Updated:	January 13, 2010
ClinicalTrials.gov Identifier:	NCT00918489 History of Changes
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Heidelberg:

soft tissue sarcoma
metastatic
vorinostat

Additional relevant MeSH terms:

Anticarcinogenic Agents
Anti-Inflammatory Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Vorinostat
Physiological Effects of Drugs
Enzyme Inhibitors
Protective Agents
Pharmacologic Actions
Neoplasms, Connective and Soft Tissue

Neoplasms
Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Sarcoma
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010