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

NCT ID: NCT00918489

Last Updated: 2018-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2013-09-30

Brief 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.

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.

Conditions

Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vorinostat

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

Group Type: EXPERIMENTAL

Vorinostat

Intervention Type: DRUG

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

Interventions

Vorinostat

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Heidelberg University

OTHER

Sponsor Role: lead

Responsible Party

Gerlinde Egerer

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gerlinde Egerer, MD

Role: STUDY_DIRECTOR

Department of Internal Medicine V, Universtity Hospital Heidelberg

Locations

Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen

Tübingen, Baden-Wurttemberg, Germany

Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover

Hanover, Niedersachen, Germany

Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf

Düsseldorf, North Rhine-Westphalia, 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

Comprehensive Cancer Center Ulm (CCCU)

Ulm, , Germany

Countries

Germany

References

Schmitt T, Mayer-Steinacker R, Mayer F, Grunwald V, Schutte J, Hartmann JT, Kasper B, Husing J, Hajda J, Ottawa G, Mechtersheimer G, Mikus G, Burhenne J, Lehmann L, Heilig CE, Ho AD, Egerer G. Vorinostat in refractory soft tissue sarcomas - Results of a multi-centre phase II trial of the German Soft Tissue Sarcoma and Bone Tumour Working Group (AIO). Eur J Cancer. 2016 Sep;64:74-82. doi: 10.1016/j.ejca.2016.05.018. Epub 2016 Jun 28.

Reference Type: DERIVED

PMID: 27367154 (View on PubMed)

Other Identifiers

SAHA-I

Identifier Type: -

Identifier Source: org_study_id