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Suberoylanilide Hydroxamic Acid in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00138203
First Posted: August 30, 2005
Last Update Posted: May 21, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
National Cancer Institute (NCI)
  Purpose
This phase II trial is studying how well suberoylanilide hydroxamic acid works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer. Drugs used in chemotherapy, such as suberoylanilide hydroxamic acid, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Suberoylanilide hydroxamic acid may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Condition Intervention Phase
Recurrent Non-small Cell Lung Cancer Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Drug: vorinostat Other: laboratory biomarker analysis Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Relapsed Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response Per RECIST Criteria [ Time Frame: Time from treatment initiation until the end of treatment. The median number of cycles was 3 (range 1-27) ]
    Per Response Evaluation Criteria In Solid Tumors and assessed by CT: 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.


Secondary Outcome Measures:
  • Time to Progression [ Time Frame: From start of treatment to progression (average was 3.7 months) ]
    Time to progression per Response Evaluation Criteria In Solid Tumors and assessed by CT: 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.

  • Overall Survial [ Time Frame: From treatment start to time of death ]
    Overall survial of subjects from the start of treatment to the time of death

  • Toxicity [ Time Frame: From first dose of treatment until 30 days from the last dose of treatment ]

Enrollment: 16
Study Start Date: June 2005
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (vorinostat)
Patients receive oral suberoylanilide hydroxamic acid once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: vorinostat
Given PO
Other Names:
  • L-001079038
  • SAHA
  • suberoylanilide hydroxamic acid
  • Zolinza
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate the response of non-small cell lung cancer to SAHA in the second line setting by applying RECIST criteria.

SECONDARY OBJECTIVES:

I. To estimate the time to progression and overall survival in this patient population.

II. To examine the toxicity profile of SAHA.

TERTIARY OBJECTIVES:

I. To evaluate the molecular activity of SAHA by evaluating its effect on histone acetylation, upregulation of target genes, generation of reactive oxygen species, apoptosis and correlation with P53 status.

II. To explore gene expression profiles that predict response to SAHA.

OUTLINE: This is a multicenter study.

Patients receive oral suberoylanilide hydroxamic acid once daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 1 month and then every 3 months for 1 year or until disease progression.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed non-small cell lung carcinoma, Stage IV (distant metastases), stage IIIB with malignant pleural effusion, or recurrent disease
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Prior therapy: no more than 1 prior cytotoxic chemotherapy regimen for their Stage IIIB/IV or recurrent disease; no previous irradiation to the only area of measurable disease, unless that site had subsequent progression of disease; radiation therapy must be completed at least 3 weeks prior to initiating study drug
  • Stage IV patients with brain metastases are eligible providing the brain metastases are clinically and radiologically stable 4 weeks after treatment with surgery and/or radiation therapy, and they are not taking steroids
  • Life expectancy greater than 3 months
  • ECOG performance status 0 or 1 (Karnofsky >= 70%)
  • Patients must have normal organ and marrow function as defined below:
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Peripheral neuropathy =< grade 1
  • Caution needs to be exercised when using SAHA with medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of SAHA; since grapefruit juice is known to interact with the CYP450 enzymes, it is recommended that patients abstain from consuming grapefruit, grapefruit juice, and other grapefruit containing products during this study
  • The effects of SAHA on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because HDAC inhibitors are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment

Exclusion Criteria:

  • Patients who have had chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 3 weeks prior to entering the study
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to SAHA
  • Any other active malignancy in the past 5 years except non-melanoma skin cancers
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with SAHA, breastfeeding should be discontinued if the mother is treated with SAHA
  • HIV-positive patients receiving combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with SAHA; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00138203


Locations
United States, Wisconsin
St. Vincent Regional Cancer Center CCOP
Green Bay, Wisconsin, United States, 54307-3508
Gundersen Lutheran
La Crosse, Wisconsin, United States, 54601
UW Health Oncology - 1 South Park
Madison, Wisconsin, United States, 53715
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Holy Family Memorial Hospital
Manitowoc, Wisconsin, United States, 54221
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Anne Traynor University of Wisconsin, Madison
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00138203     History of Changes
Other Study ID Numbers: NCI-2012-03070
NCI-2012-03070 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CO 04510 ( Other Identifier: University of Wisconsin Hospital and Clinics )
6860 ( Other Identifier: CTEP )
P30CA014520 ( U.S. NIH Grant/Contract )
U01CA062491 ( U.S. NIH Grant/Contract )
First Submitted: August 29, 2005
First Posted: August 30, 2005
Results First Submitted: February 13, 2013
Results First Posted: May 21, 2014
Last Update Posted: May 21, 2014
Last Verified: December 2012

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
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action