Clinical trial NCT00918489: Study on Efficacy and Tolerability of Vorinostat in Patients With Advanced, Metastatic Soft Tissue Sarcoma (STS)
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Keywords: soft tissue sarcoma
metastatic
vorinostat
Lead sponsor: Heidelberg University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2009-06-11
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Evaluation of the efficacy of vorinostat on the basis of progression free survival (PFS) up to 1 year after first administration of the IMP.
timeFrame: Up to 1 year
Secondary outcomes:
measure: 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.
timeFrame: Up to 1 year
Other outcomes:
Locations:
city: Tübingen
country: Germany
facility: Department of Hematology, Oncology, Rheumatology and Immunology, University Hospital Tübingen
state: Baden-Württemberg
city: Hannover
country: Germany
facility: Department of Hematology, Hemostaseology, Oncology and Stemm Cell Transplantation, Medical School Hannover
state: Niedersachen
city: Düsseldorf
country: Germany
facility: Department of Oncology, Hematology and Palliative Medicine, Marien Hospital Düsseldorf
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Comprehensive Cancer Center North, University Hospital Kiel
city: Mannheim
country: Germany
facility: Sarcoma Center Mannheim, University Hospital Mannheim
city: Tübingen
country: Germany
facility: Center for Soft Tissue Sarcoma, University Hospital Tübingen
city: Ulm
country: Germany
facility: Comprehensive Cancer Center Ulm (CCCU)
Study officials:
affiliation: Department of Internal Medicine V, Universtity Hospital Heidelberg
name: Gerlinde Egerer, MD
role: STUDY_DIRECTOR
References:
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.