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

Phase 2

Completed

• Conditions: Stage IV Non-small Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer
• Interventions: Drug: vorinostat; Other: laboratory biomarker analysis

• Registration Number: NCT00138203
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study Start: 2005-06
• Study First Submitted: 2005-08-29
• Study First Submitted QC: 2005-08-29
• Study First Posted: 2005-08-30
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Results First Submitted: 2013-02-13
• Results First Submitted QC: 2014-04-25
• Results First Posted: 2014-05-21
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-03
• Last Update Posted: 2018-01-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (vorinostat)	laboratory biomarker analysis	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.
Treatment (vorinostat)	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.

Primary Outcome Measures

Name	Time	Method
Response Per RECIST Criteria	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

Name	Time	Method
Time to Progression	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.
Toxicity	From first dose of treatment until 30 days from the last dose of treatment	Number of participants experiencing adverse events possibly related to SAHA from first dose of treatment until 30 days from the last dose of treatment.
Overall Survial	From treatment start to time of death	Overall survial of subjects from the start of treatment to the time of death

Trial Locations

Locations (5)

University of Wisconsin Hospital and Clinics; 🇺🇸 Madison, Wisconsin, United States

Gundersen Lutheran; 🇺🇸 La Crosse, Wisconsin, United States

Holy Family Memorial Hospital; 🇺🇸 Manitowoc, Wisconsin, United States

UW Health Oncology - 1 South Park; 🇺🇸 Madison, Wisconsin, United States

St. Vincent Regional Cancer Center CCOP; 🇺🇸 Green Bay, Wisconsin, United States