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

Carcinoma, Non Small Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00798720
• Other study ID #: CO08502
• Secondary ID: H-2008-0229A5342
• Status: Completed
• Phase: Phase 2
• Start date: December 2008
• Est. completion date: October 2012

Study information

• Verified date: September 2016
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Carcinoma, Non Small Cell Lung
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• vorinostat
400 mg by mouth once daily for days 1-14 of each 21 day cycle
• bortezomib
1.3 mg/m2 IV on days 1, 4, 8, 11 of each 21 day cycle

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Merck Sharp & Dohme Corp., Millennium Pharmaceuticals, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Median Overall Survival		5 years
Secondary	Toxicity	Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0	30 days post-treatment