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

Primary Purpose

Soft Tissue Sarcoma

Status

Completed

Phase

Phase 2

Locations

Germany

Study Type

Interventional

Intervention

Vorinostat

About this trial

This is an interventional treatment trial for Soft Tissue Sarcoma focused on measuring soft tissue sarcoma, metastatic, vorinostat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen
Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover
Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf
Comprehensive Cancer Center North, University Hospital Kiel
Sarcoma Center Mannheim, University Hospital Mannheim
Center for Soft Tissue Sarcoma, University Hospital Tübingen
Comprehensive Cancer Center Ulm (CCCU)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Vorinostat

Arm Description

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

Outcomes

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.

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.

Full Information

NCT ID

NCT00918489

First Posted

June 10, 2009

Last Updated

October 15, 2018

Sponsor

Heidelberg University

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT00918489

Brief Title

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

Acronym

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2018

Overall Recruitment Status

Completed

Study Start Date

May 2010 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Heidelberg University

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Soft Tissue Sarcoma

Keywords

soft tissue sarcoma, metastatic, vorinostat

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vorinostat

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Vorinostat

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

Time Frame

Up to 1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gerlinde Egerer, MD

Organizational Affiliation

Department of Internal Medicine V, Universtity Hospital Heidelberg

Official's Role

Study Director

Facility Information:

Facility Name

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

City

Tübingen

State/Province

Baden-Württemberg

ZIP/Postal Code

D-72076

Country

Germany

Facility Name

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

City

Hannover

State/Province

Niedersachen

ZIP/Postal Code

D-30625

Country

Germany

Facility Name

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

City

Düsseldorf

State/Province

Nordrhein-Westfalen

ZIP/Postal Code

D-40479

Country

Germany

Facility Name

Comprehensive Cancer Center North, University Hospital Kiel

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

Sarcoma Center Mannheim, University Hospital Mannheim

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Center for Soft Tissue Sarcoma, University Hospital Tübingen

City

Tübingen

ZIP/Postal Code

72074

Country

Germany

Facility Name

Comprehensive Cancer Center Ulm (CCCU)

City

Ulm

ZIP/Postal Code

89081

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

27367154

Citation

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.

Results Reference

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

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