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CompletedNCT00937495Updated May 14, 2014Results posted

Vorinostat and Bortezomib in Treating Patients With Advanced Soft Tissue Sarcoma

A Phase 2 interventional study of vorinostat and bortezomib in Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma and Stage IV Adult Soft Tissue Sarcoma, sponsored by National Cancer Institute (NCI). Completed at 6 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-05-14.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
16
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.)

02

Conditions studied

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

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03

In context

Sarcoma

1,667 studies on the registry are indexed under Sarcoma; 393 are open to participants now.

This study's enrollment of 16 is below the median of 40 across 1,283 interventional studies indexed under Sarcoma.

Browse Sarcoma studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
16 participants (actual)

Study arms

  • 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.

    Drug: vorinostat · Drug: bortezomib

Interventions

  • Drugvorinostat

    400 mg given PO

    Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

  • Drugbortezomib

    1.3 mg/m\^2 given IV

    Also known as: LDP 341, MLN341, VELCADE

06

What researchers measure

Primary outcomes

  1. Confirmed Tumor Responses

    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.

    Time frame: Up to 2 years

Secondary outcomes

  1. Progression Free Survival

    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.

    Time frame: Up to 2 years

  2. Overall Survival

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Time frame: Time from registration to death due to any cause, assessed up to 2 years

07

Results

Posted Nov 21, 2013

Participant flow

Sixteen patients were accrued to this study from June 2009 through July 2010.

Participant flow — Overall Study
MilestoneTreatment (Vorinostat, Bortezomib)
Started16
Completed14
Not completed2
Withdrew: Protocol violation2

Outcome measures

PrimaryConfirmed Tumor Responses

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.

Time frame:
Up to 2 years
Reported as:
Number · participants
Confirmed Tumor Responses
participantsTreatment (Vorinostat, Bortezomib)
Complete Response (CR)0
Partial Response (PR)0
SecondaryProgression Free Survival

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.

Time frame:
Up to 2 years
Reported as:
Median · months
Progression Free Survival
monthsTreatment (Vorinostat, Bortezomib)
Progression Free Survival1.5 (1.3 to 2.9)
SecondaryOverall Survival

The distribution of survival time will be estimated using the method of Kaplan-Meier.

Time frame:
Time from registration to death due to any cause, assessed up to 2 years
Reported as:
Median · months
Overall Survival
monthsTreatment (Vorinostat, Bortezomib)
Overall Survival16.4 (9.4 to NA)

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Vorinostat, Bortezomib)—6/16 (37.5%)16/16 (100%)
Most frequent serious events
Showing 10 of 14
Most frequent serious events
EventTreatment (Vorinostat, Bortezomib)
DiarrheaGastrointestinal disorders3/16
Platelet count decreasedInvestigations3/16
VomitingGastrointestinal disorders2/16
Hemoglobin decreasedBlood and lymphatic system disorders1/16
NauseaGastrointestinal disorders1/16
FatigueGeneral disorders1/16
INR increasedInvestigations1/16
AnorexiaMetabolism and nutrition disorders1/16
DehydrationMetabolism and nutrition disorders1/16
Depressed level of consciousnessNervous system disorders1/16
Most frequent other events
Showing 10 of 39
Most frequent other events
EventTreatment (Vorinostat, Bortezomib)
FatigueGeneral disorders15/16
NauseaGastrointestinal disorders14/16
Platelet count decreasedInvestigations13/16
Hemoglobin decreasedBlood and lymphatic system disorders12/16
DiarrheaGastrointestinal disorders12/16
VomitingGastrointestinal disorders11/16
Leukocyte count decreasedInvestigations9/16
AnorexiaMetabolism and nutrition disorders9/16
Aspartate aminotransferase increasedInvestigations5/16
Peripheral sensory neuropathyNervous system disorders5/16

Baseline characteristics

Age, Continuous
Age, Continuous(years)Treatment (Vorinostat, Bortezomib)
Median62 (34 to 81)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Vorinostat, Bortezomib)
Female11
Male5
Region of Enrollment
Region of Enrollment(participants)Treatment (Vorinostat, Bortezomib)
United States16
08

Study locations

6 sites
  • Mayo Clinic in Florida
    Jacksonville, Florida 32224-9980, United States
  • Johns Hopkins University
    Baltimore, Maryland 21287-8936, United States
  • Mayo Clinic
    Rochester, Minnesota 55905, United States
  • Metro-Minnesota CCOP
    Saint Louis Park, Minnesota 55416, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • University of Wisconsin Hospital and Clinics
    Madison, Wisconsin 53792, United States
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 14, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00937495
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jul 13, 2009
Start date
Jun 2009
Primary completion
Aug 2010
Completion
Jun 2011
Results posted
Nov 21, 2013
Last update
May 14, 2014

Study contacts

Steven Attia
principal investigator · Mayo Clinic
View the source record on ClinicalTrials.gov ↗

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