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

Study Overview
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Brief Summary
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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
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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

Official Title
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Phase II Study of Vorinostat (SAHA, Zolinza) and Bortezomib (PS341, Velcade) as Third-Line Treatment in Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non Small Cell Lung

Intervention / Treatment
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* Drug: vorinostat
* Drug: bortezomib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorinostat + Bortezomib<br>Vorinostat 400 mg + Bortezomib 1.3 mg/m2 | Drug: vorinostat<br>* 400 mg by mouth once daily for days 1-14 of each 21 day cycle<br>* Other names: Zolinza;Drug: bortezomib<br>* 1.3 mg/m2 IV on days 1, 4, 8, 11 of each 21 day cycle<br>* Other names: Velcade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Three-months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Until disease progression, up to 2 years | 
| Median Overall Survival |  | 5 years | 
| Toxicity | Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 | 30 days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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non small cell lung cancer, HDAC, proteasome inhibitor