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
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
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
NCT ID
NCT00798720
First Posted
November 25, 2008
Last Updated
December 11, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
Millennium Pharmaceuticals, Inc., Merck Sharp & Dohme LLC
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
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