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Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00937495
First received: July 10, 2009
Last updated: April 25, 2014
Last verified: September 2013

July 10, 2009
April 25, 2014
June 2009
August 2010   (final data collection date for primary outcome measure)
Confirmed Tumor Responses [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

The number of confirmed tumor responses is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) on two consecutive evaluations at least six weeks apart.

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest dimension (LD) of target lesions taking as reference the baseline sum LD.

Objective response rate (complete response or partial response) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00937495 on ClinicalTrials.gov Archive Site
  • Progression Free Survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Progression-free survival is defined as the time from registration to the time of progression or death, whichever comes first. The distribution and median of progression-free survival times will be estimated using the method of Kaplan-Meier.
  • Overall Survival [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of survival time will be estimated using the method of Kaplan-Meier.
  • Adverse events [ Designated as safety issue: Yes ]
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma
A Phase II Study of Suberoylanilide Hydroxamic Acid and Bortezomib in Advanced Soft Tissue Sarcomas

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.

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.)

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Drug: vorinostat
    400 mg given PO
    Other Names:
    • L-001079038
    • SAHA
    • suberoylanilide hydroxamic acid
    • Zolinza
  • Drug: bortezomib
    1.3 mg/m^2 given IV
    Other Names:
    • LDP 341
    • MLN341
    • VELCADE
Experimental: Treatment (vorinostat, bortezomib)
Patients receive 400 mg vorinostat orally once daily on days 1-14. Patients also receive 1.3 mg/m^2 bortezomib 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.
Interventions:
  • Drug: vorinostat
  • Drug: bortezomib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
June 2011
August 2010   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00937495
NCI-2011-03810, MC0778, CDR0000646715, MAYO-MC0778, N01CM62205
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Steven Attia Mayo Clinic
National Cancer Institute (NCI)
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP