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

University of Wisconsin (UW)

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Non Small Cell Lung

Treatments: Drug: bortezomib; Drug: vorinostat

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00798720

H-2008-0229 (Other Identifier)

A534260 (Other Identifier)

NCI-2011-00811 (Registry Identifier)

SMPH\MEDICINE\HEM-ONC (Other Identifier)

CO08502

Details and patient eligibility

About

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.

Full 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

Enrollment: 18 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 1 patient group

Vorinostat + Bortezomib

Experimental group

Description:

Vorinostat 400 mg + Bortezomib 1.3 mg/m2

Treatment:

Drug: vorinostat

Drug: bortezomib