Clinical trial NCT00937495: Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma
Official title: A Phase II Study of Suberoylanilide Hydroxamic Acid and Bortezomib in Advanced Soft Tissue Sarcomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2009-07-13
Enrollment: 16
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: 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.

Detailed description: PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.)

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

Primary outcomes:
measure: Confirmed Tumor Responses
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Time from registration to death due to any cause, assessed up to 2 years
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic in Florida
state: Florida
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota CCOP
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
Study officials:
affiliation: Mayo Clinic
name: Steven Attia
role: PRINCIPAL_INVESTIGATOR
References: