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

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

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.

Study Overview

• Status: Completed
• Conditions: Soft Tissue Sarcoma
• Intervention / Treatment: Drug: Vorinostat

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany, 24105
    • Comprehensive Cancer Center North, University Hospital Kiel
  • Mannheim, Germany, 68167
    • Sarcoma Center Mannheim, University Hospital Mannheim
  • Tübingen, Germany, 72074
    • Center for Soft Tissue Sarcoma, University Hospital Tübingen
  • Ulm, Germany, 89081
    • Comprehensive Cancer Center Ulm (CCCU)
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, D-72076
      • Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen
  • Niedersachen
    • Hannover, Niedersachen, Germany, D-30625
      • Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover
  • Nordrhein-Westfalen
    • Düsseldorf, Nordrhein-Westfalen, Germany, D-40479
      • Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vorinostat; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Heidelberg University
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Gerlinde Egerer, MD, Department of Internal Medicine V, Universtity Hospital Heidelberg

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): September 1, 2013

Study Registration Dates

• First Submitted: June 10, 2009
• First Submitted That Met QC Criteria: June 10, 2009
• First Posted (ESTIMATE): June 11, 2009

Study Record Updates

• Last Update Posted (ACTUAL): October 17, 2018
• Last Update Submitted That Met QC Criteria: October 15, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: metastatic; soft tissue sarcoma; vorinostat
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Vorinostat
• Other Study ID Numbers: SAHA-I