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

• ClinicalTrials.gov Identifier: NCT00798720
• Recruitment Status: Completed
• First Posted: November 26, 2008
• Results First Posted: November 21, 2016
• Last Update Posted: December 13, 2019
• Sponsor: University of Wisconsin, Madison
• Collaborators: Millennium Pharmaceuticals, Inc.; Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): University of Wisconsin, Madison

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non Small Cell Lung	Drug: vorinostat; Drug: bortezomib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: December 2008
• Actual Primary Completion Date: October 2012
• Actual Study Completion Date: October 2012

Arms and Interventions

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: PS341; Velcade

Outcome Measures

Primary Outcome Measures :

1. Three-month Progression-free Survival [ Time Frame: 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 :

1. Response Rate [ Time Frame: 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.
2. Median Overall Survival [ Time Frame: 5 years ]
3. Toxicity [ Time Frame: 30 days post-treatment ]
   Graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Eligibility Criteria

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

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

Contacts and Locations

Sponsors and Collaborators

University of Wisconsin, Madison

Millennium Pharmaceuticals, Inc.

Merck Sharp & Dohme Corp.

Investigators

• Principal Investigator: Tien Hoang, M.D.; University of Wisconsin, Madison

More Information

• Responsible Party: University of Wisconsin, Madison
• ClinicalTrials.gov Identifier: NCT00798720
• Other Study ID Numbers: CO08502; H-2008-0229 ( Other Identifier: Institutional Review Board ); A534260 ( Other Identifier: UW Madison ); SMPH\MEDICINE\HEM-ONC ( Other Identifier: UW Madison ); NCI-2011-00811 ( Registry Identifier: NCI Trial ID )
• First Posted: November 26, 2008
• Results First Posted: November 21, 2016
• Last Update Posted: December 13, 2019
• Last Verified: September 2016

Keywords provided by University of Wisconsin, Madison:

non small cell lung cancer; HDAC; proteasome inhibitor

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Bortezomib; Vorinostat; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action