Clinical trial NCT00798720: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Non Small Cell Lung
Keywords: non small cell lung cancer
HDAC
proteasome inhibitor
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Millennium Pharmaceuticals, Inc.
name: Merck Sharp & Dohme LLC
First posted: 2008-11-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Three-month Progression-free Survival
timeFrame: Three-months post-treatment
Secondary outcomes:
measure: Response Rate
timeFrame: Until disease progression, up to 2 years
measure: Median Overall Survival
timeFrame: 5 years
measure: Toxicity
timeFrame: 30 days post-treatment
Other outcomes:
Locations:
Study officials:
affiliation: University of Wisconsin, Madison
name: Tien Hoang, M.D.
role: PRINCIPAL_INVESTIGATOR
References: