Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma
Condition: Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma
MeSH terms: Sarcoma
Intervention: vorinostat; bortezomib
Intervention description: 400 mg given PO; 1.3 mg/m^2 given IV
Intervention MeSH terms: Bortezomib; Vorinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well giving vorinostat together with bortezomib works in
      treating patients with advanced soft tissue sarcoma. Vorinostat and bortezomib may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving
      vorinostat together with bortezomib may kill more tumor cells.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed advanced, unresectable, or metastatic soft
             tissue sarcoma (STS)

          -  Measurable disease, defined as >= 1 lesion that can be accurately measured in >= 1
             dimension as >= 2 cm by conventional techniques OR >= 1 cm by spiral computed
             tomography (CT) scan

          -  No small round cell tumors, including the following:

               -  Primitive neuroectodermal tumor

               -  Rhabdomyosarcoma

               -  Ewing sarcoma

               -  Osteosarcoma

          -  No known active and/or untreated brain metastases and/or brain metastases requiring
             ongoing therapy (e.g., corticosteroids)

               -  Treated, inactive brain metastases not requiring ongoing therapy allowed provided
                  the brain metastases have been stable for >= 1 month as assessed by intracranial
                  imaging AND there is no indication of increased vascularity of the treated
                  metastases within 14 days before study entry as assessed by magnetic resonance
                  imaging (MRI)

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS
             70-100%

          -  Life expectancy >= 12 weeks

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Total bilirubin normal

          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 2.5 times
             upper limit of normal

          -  Creatinine normal OR creatinine clearance >= 60 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  Able to take oral medication

          -  No peripheral neuropathy >= grade 2

          -  No concurrent uncontrolled illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia or myocardial infarction within the past 6 months

               -  Psychiatric illness and/or social situation that would limit compliance with
                  study requirements

          -  No history of Torsades de Pointes

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to vorinostat or bortezomib

          -  No more than 1 prior systemic treatment for advanced STS, including investigational
             agents

               -  Adjuvant therapy is not considered a systemic regimen

          -  More than 2 weeks since prior valproic acid

          -  More than 4 weeks since prior and no concurrent chemotherapy (> 6 weeks for
             nitrosoureas or mitomycin C) or radiotherapy and recovered

               -  Radiotherapy to bone metastasis within the past 2 weeks allowed provided there is
                  active non-bone disease outside the radiation port

          -  No prior radiotherapy to >= 33% of the bone marrow

          -  No prior vorinostat or bortezomib

          -  No concurrent category I medications that are generally accepted to have a risk of
             causing Torsades de Pointes, including any of the following:

               -  Quinidine, procainamide, disopyramide

               -  Amiodarone, sotalol, ibutilide, dofetilide

               -  Erythromycin, clarithromycin

               -  Chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide, cisapride,
                  bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine,
                  levomethadyl, pentamidine, sparfloxacin, lidoflazine

          -  No concurrent combination antiretroviral therapy for human immunodeficiency virus
             (HIV)-positive patients

          -  No other concurrent investigational agents for the primary malignancy

          -  No other concurrent anticancer therapy