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A Phase II Study of Suberoylanilide Hydroxamic Acid and Bortezomib in Advanced Soft Tissue Sarcomas

Phase 2
18 Years
Open (Enrolling)
Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

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Trial Information

A Phase II Study of Suberoylanilide Hydroxamic Acid and Bortezomib in Advanced Soft Tissue Sarcomas


I. To determine the objective response rate in patients with advanced soft tissue sarcoma
treated with vorinostat and bortezomib.


I. Characterize the toxicity of this regimen in these patients. II. Evaluate the
progression-free survival and median overall survival of patients treated with this regimen.


Patients receive vorinostat orally (PO) once daily on days 1-14. Patients also receive
bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every
21 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 6 months for up to 2
years. (As of Addendum 7, patient follow-up no longer required.)

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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed response rate defined as completer response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST)

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Steven Attia

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

June 2009

Completion Date:

Related Keywords:

  • Recurrent Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Sarcoma



Johns Hopkins University Baltimore, Maryland  21205
Mayo Clinic Rochester, Minnesota  55905
Washington University School of Medicine Saint Louis, Missouri  63110
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Mayo Clinic in Florida Jacksonville, Florida  32224
Metro-Minnesota CCOP St. Louis Park, Minnesota