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

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

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non Small Cell Lung
• Intervention / Treatment: Drug: vorinostat; Drug: bortezomib

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vorinostat + Bortezomib; Vorinostat 400 mg + Bortezomib 1.3 mg/m2	Drug: vorinostat; 400 mg by mouth once daily for days 1-14 of each 21 day cycle; Other Names: SAHA; Zolinza; Drug: bortezomib; 1.3 mg/m2 IV on days 1, 4, 8, 11 of each 21 day cycle; Other Names: Velcade; PS341

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: Merck Sharp & Dohme LLC; Millennium Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Tien Hoang, M.D., University of Wisconsin, Madison

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: November 25, 2008
• First Submitted That Met QC Criteria: November 25, 2008
• First Posted (Estimate): November 26, 2008

Study Record Updates

• Last Update Posted (Actual): December 13, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: proteasome inhibitor; non small cell lung cancer; HDAC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Bortezomib; Vorinostat
• Other Study ID Numbers: CO08502; A534260 (Other Identifier: UW Madison); SMPH\MEDICINE\HEM-ONC (Other Identifier: UW Madison); H-2008-0229 (Other Identifier: Institutional Review Board); NCI-2011-00811 (Registry Identifier: NCI Trial ID)