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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00798720
Recruitment Status : Completed
First Posted : November 26, 2008
Results First Posted : November 21, 2016
Last Update Posted : November 21, 2016
Millennium Pharmaceuticals, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
University of Wisconsin, Madison

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Non Small Cell Lung Drug: vorinostat Drug: bortezomib Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2008
Actual Primary Completion Date : October 2012
Actual Study Completion Date : October 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Vorinostat + Bortezomib
Vorinostat 400 mg + Bortezomib 1.3 mg/m2
Drug: vorinostat
400 mg by mouth once daily for days 1-14 of each 21 day cycle
Other Names:
  • SAHA
  • Zolinza

Drug: bortezomib
1.3 mg/m2 IV on days 1, 4, 8, 11 of each 21 day cycle
Other Names:
  • PS341
  • Velcade

Primary Outcome Measures :
  1. Three-month Progression-free Survival [ Time Frame: Three-months post-treatment ]
    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 :
  1. Response Rate [ Time Frame: Until disease progression, up to 2 years ]
    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.

  2. Median Overall Survival [ Time Frame: 5 years ]
  3. Toxicity [ Time Frame: 30 days post-treatment ]
    Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00798720

Sponsors and Collaborators
University of Wisconsin, Madison
Millennium Pharmaceuticals, Inc.
Merck Sharp & Dohme Corp.
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Principal Investigator: Tien Hoang, M.D. University of Wisconsin, Madison

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Responsible Party: University of Wisconsin, Madison Identifier: NCT00798720     History of Changes
Other Study ID Numbers: H-2008-0229
First Posted: November 26, 2008    Key Record Dates
Results First Posted: November 21, 2016
Last Update Posted: November 21, 2016
Last Verified: September 2016

Keywords provided by University of Wisconsin, Madison:
non small cell lung cancer
proteasome inhibitor

Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action