search
Back to results

Vorinostat and Bortezomib as Third-line Treatment in Advanced Non-small Cell Lung Cancer

Primary Purpose

Carcinoma, Non Small Cell Lung

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
vorinostat
bortezomib
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non Small Cell Lung focused on measuring non small cell lung cancer, HDAC, proteasome inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Pathologically/histologically confirmed NSCLC
  • Advance NSCLC (stage IIIB w/ effusion, stage IV, or recurrent disease)
  • Measurable disease
  • Two prior systemic anti-cancer (cytotoxic or biologic) regimens for advanced/metastatic disease, including one (1) platinum-based chemotherapy
  • Prior treatment allowed if side effects have resolved and 3 weeks has passed since last dose of treatment (1 week for palliative radiation therapy)
  • ECOG performance status 0, 1, or 2
  • Patients with brain metastases are allowed, if clinically stable after treatment
  • Normal liver, kidney, and marrow function
  • 18 years of age or older
  • Negative pregnancy test for women of child-bearing potential.
  • Life expectancy 3 months or more
  • No concurrent use of other antitumor agents

Exclusion Criteria:

  • Prior therapy with vorinostat, HDAC inhibitors, or bortezomib
  • Pre-existing neuropathy grade >/= 2
  • Myocardial infarction within 6 months prior to enrollment or have NY Heart Association Class III or Class IV heart failure
  • Have taken valproic acid </= 4 weeks prior to enrollment
  • Previous or current malignancies of other histologies within the past 5 years, except cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
  • Hypersensitivity to bortezomib, boron, or mannitol
  • Serious medical or psychiatric illness likely to interfere with participation in the clinical study
  • Pregnant women
  • HIV positive patients
  • Hepatitis infection (HCV or HBV) patients

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Vorinostat + Bortezomib

    Arm Description

    Vorinostat 400 mg + Bortezomib 1.3 mg/m2

    Outcomes

    Primary Outcome Measures

    Three-month Progression-free Survival
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new lesions."

    Secondary Outcome Measures

    Response Rate
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI, CT, or chest x-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
    Median Overall Survival
    Toxicity
    Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

    Full Information

    First Posted
    November 25, 2008
    Last Updated
    December 11, 2019
    Sponsor
    University of Wisconsin, Madison
    Collaborators
    Millennium Pharmaceuticals, Inc., Merck Sharp & Dohme LLC
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT00798720
    Brief Title
    Vorinostat and Bortezomib as Third-line Treatment in Advanced Non-small Cell Lung Cancer
    Official Title
    Phase II Study of Vorinostat (SAHA, Zolinza) and Bortezomib (PS341, Velcade) as Third-Line Treatment in Patients With Advanced Non-Small Cell Lung Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2016
    Overall Recruitment Status
    Completed
    Study Start Date
    December 2008 (undefined)
    Primary Completion Date
    October 2012 (Actual)
    Study Completion Date
    October 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    University of Wisconsin, Madison
    Collaborators
    Millennium Pharmaceuticals, Inc., Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of this study is to evaluate the efficacy of vorinostat and bortezomib in the third line treatment of advanced NSCLC, as well as to assess toxicity (including neuropathy) and tolerability of this regimen.
    Detailed Description
    Current treatment for non-small cell lung cancer (NSCLC) remains inadequate. Vorinostat is a novel agent that inhibits the enzymatic activity of histone deacetylases (HDACs). Bortezomib is a small molecule proteasome inhibitor. Preclinical and clinical studies have shown the advantages of combining these two agents in the treatment of NSCLC

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Carcinoma, Non Small Cell Lung
    Keywords
    non small cell lung cancer, HDAC, proteasome inhibitor

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    18 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Vorinostat + Bortezomib
    Arm Type
    Experimental
    Arm Description
    Vorinostat 400 mg + Bortezomib 1.3 mg/m2
    Intervention Type
    Drug
    Intervention Name(s)
    vorinostat
    Other Intervention Name(s)
    SAHA, Zolinza
    Intervention Description
    400 mg by mouth once daily for days 1-14 of each 21 day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    bortezomib
    Other Intervention Name(s)
    PS341, Velcade
    Intervention Description
    1.3 mg/m2 IV on days 1, 4, 8, 11 of each 21 day cycle
    Primary Outcome Measure Information:
    Title
    Three-month Progression-free Survival
    Description
    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new lesions."
    Time Frame
    Three-months post-treatment
    Secondary Outcome Measure Information:
    Title
    Response Rate
    Description
    Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by MRI, CT, or chest x-ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.
    Time Frame
    Until disease progression, up to 2 years
    Title
    Median Overall Survival
    Time Frame
    5 years
    Title
    Toxicity
    Description
    Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
    Time Frame
    30 days post-treatment

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Pathologically/histologically confirmed NSCLC Advance NSCLC (stage IIIB w/ effusion, stage IV, or recurrent disease) Measurable disease Two prior systemic anti-cancer (cytotoxic or biologic) regimens for advanced/metastatic disease, including one (1) platinum-based chemotherapy Prior treatment allowed if side effects have resolved and 3 weeks has passed since last dose of treatment (1 week for palliative radiation therapy) ECOG performance status 0, 1, or 2 Patients with brain metastases are allowed, if clinically stable after treatment Normal liver, kidney, and marrow function 18 years of age or older Negative pregnancy test for women of child-bearing potential. Life expectancy 3 months or more No concurrent use of other antitumor agents Exclusion Criteria: Prior therapy with vorinostat, HDAC inhibitors, or bortezomib Pre-existing neuropathy grade >/= 2 Myocardial infarction within 6 months prior to enrollment or have NY Heart Association Class III or Class IV heart failure Have taken valproic acid </= 4 weeks prior to enrollment Previous or current malignancies of other histologies within the past 5 years, except cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin Hypersensitivity to bortezomib, boron, or mannitol Serious medical or psychiatric illness likely to interfere with participation in the clinical study Pregnant women HIV positive patients Hepatitis infection (HCV or HBV) patients
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Tien Hoang, M.D.
    Organizational Affiliation
    University of Wisconsin, Madison
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    Vorinostat and Bortezomib as Third-line Treatment in Advanced Non-small Cell Lung Cancer

    We'll reach out to this number within 24 hrs