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

Phase 2

Completed

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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Vorinostat + Bortezomib	vorinostat	Vorinostat 400 mg + Bortezomib 1.3 mg/m2
Vorinostat + Bortezomib	bortezomib	Vorinostat 400 mg + Bortezomib 1.3 mg/m2

Primary Outcome Measures

Name	Time	Method
Three-month Progression-free Survival	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

Name	Time	Method
Toxicity	30 days post-treatment	Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0
Response Rate	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.
Median Overall Survival	5 years