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

Primary Purpose

Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
vorinostat
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Non-small Cell Lung Cancer

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St. Vincent Regional Cancer Center CCOP
  • Gundersen Lutheran
  • UW Health Oncology - 1 South Park
  • University of Wisconsin Hospital and Clinics
  • Holy Family Memorial Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (vorinostat)

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Per RECIST Criteria
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 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
Overall survial of subjects from the start of treatment to the time of death
Toxicity
Number of participants experiencing adverse events possibly related to SAHA from first dose of treatment until 30 days from the last dose of treatment.

Full Information

First Posted
August 29, 2005
Last Updated
January 3, 2018
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00138203
Brief Title
Suberoylanilide Hydroxamic Acid in Treating Patients With Stage IIIB, Stage IV, or Recurrent Non-Small Cell Lung Cancer
Official Title
A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Relapsed Non-small Cell Lung Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
June 2005 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (vorinostat)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
vorinostat
Other Intervention Name(s)
L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Response Per RECIST Criteria
Description
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.
Time Frame
Time from treatment initiation until the end of treatment. The median number of cycles was 3 (range 1-27)
Secondary Outcome Measure Information:
Title
Time to Progression
Description
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.
Time Frame
From start of treatment to progression (average was 3.7 months)
Title
Overall Survial
Description
Overall survial of subjects from the start of treatment to the time of death
Time Frame
From treatment start to time of death
Title
Toxicity
Description
Number of participants experiencing adverse events possibly related to SAHA from first dose of treatment until 30 days from the last dose of treatment.
Time Frame
From first dose of treatment until 30 days from the last dose of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Traynor
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Vincent Regional Cancer Center CCOP
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54307-3508
Country
United States
Facility Name
Gundersen Lutheran
City
La Crosse
State/Province
Wisconsin
ZIP/Postal Code
54601
Country
United States
Facility Name
UW Health Oncology - 1 South Park
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53715
Country
United States
Facility Name
University of Wisconsin Hospital and Clinics
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Holy Family Memorial Hospital
City
Manitowoc
State/Province
Wisconsin
ZIP/Postal Code
54221
Country
United States

12. IPD Sharing Statement

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

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