Vorinostat, Paclitaxel, and Radiation Therapy in Treating Patients Unable to Tolerate Cisplatin With Stage III Non-Small Lung Cancer That Cannot Be Removed By Surgery

NCT ID: NCT00662311

Last Updated: 2017-06-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2011-09-30

Brief Summary

This phase I/II trial studies the side effects and best dose of vorinostat when given together with paclitaxel and radiation therapy and to see how well it works in treating patients unable to tolerate cisplatin with stage III non-small cell lung cancer (NSCLC) that cannot be removed by surgery. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving vorinostat together with paclitaxel and radiation therapy may kill more tumor cells

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.

SECONDARY OBJECTIVES:

I. To assess the safety and toxicity of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.

II. To determine the radiological response rate, by computed tomography (CT) scan, of vorinostat when administered in combination with paclitaxel and thoracic radiation therapy in patients with locally advanced NSCLC.

III. To describe the progression free survival (PFS) and overall survival (OS) of this regiment over 3 years of follow up.

OUTLINE: This is a phase I, dose-escalation study of vorinostat followed by a phase II study.

Patients receive vorinostat orally (PO) once daily (QD), 5 days a week and paclitaxel intravenously (IV) over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, 12 weeks, every 3 months for 2 years, and then every 6 months for 1 year.

Conditions

Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (vorinostat with paclitaxel and radiotherapy)

Patients receive vorinostat PO QD, 5 days a week and paclitaxel IV over 1 hour once a week. Patients also undergo radiation therapy QD, 5 days a week. Treatment repeats every week for 7 courses in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

vorinostat

Intervention Type: DRUG

Given PO

paclitaxel

Intervention Type: DRUG

Given IV

radiation therapy

Intervention Type: RADIATION

Undergo radiation therapy

Interventions

vorinostat

Given PO

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

radiation therapy

Undergo radiation therapy

Intervention Type: RADIATION

Other Intervention Names

L-001079038; SAHA; suberoylanilide hydroxamic acid; Zolinza; Anzatax; Asotax; TAX; Taxol; irradiation; radiotherapy; therapy, radiation

Eligibility Criteria

Inclusion Criteria

• Histologically or cytologically proven diagnosis of NSCLC
• Inoperable Stage IIIA or IIIB (excluding malignant pleural effusion) disease according to the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, Sixth edition (2002)
• At least one site of measurable disease, as defined by the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Inability to tolerate full dose cisplatin as defined by:
• Creatinine clearance less than 50ml/min
• Greater than grade 2 sensory hearing loss (as defined by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] criteria v3.0 adverse event term "Hearing: Patients without baseline audiogram and not enrolled in a monitoring program")
• Performance status >= 2
• Age >= 75 years
• Cardiac history, such as myocardial infarction within 6 months, angina, or heart disease as defined by the New York Heart Association (NYHA) Class III or IV
• Any other comorbid disease or condition that would increase the risk of toxicity of cisplatin therapy
• Female patient is either post menopausal, free from menses for >= 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study
• Female patient of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG) within 7 days prior to receiving the first dose of vorinostat
• Male patient agrees to use an adequate method of contraception for the duration of the study
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Platelets >= 100,000/mcL
• Hemoglobin >= 9 g/dL
• Prothrombin Time or International Normalized Ratio (INR) =< 1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation
• Partial thromboplastin time (PTT) =< 1.2 times the ULN unless the patient is receiving therapeutic anticoagulation
• Potassium levels: Normal limits
• Magnesium levels: Normal limits
• Calculated creatinine clearance >= 20 mL/min
• Serum total bilirubin =< 1.5 X ULN
• Aspartate aminotransferase (AST) (serum glutamate oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN
• Alkaline Phosphatase =< 2.5 X ULN
• Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent
• Patient has a life expectancy of at least 12 weeks
• Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study

Exclusion Criteria

• Patient who has had chemotherapy, radiotherapy, or biological therapy for NSCLC within 5 years prior to initial dosing with study drug(s)
• Symptomatic neuropathy (>= grade 2)
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s)
• Patient had prior treatment with an histone deacetylases (HDAC) inhibitor (e.g., romidespsin [Depsipeptide, NSC-630176], entinostat [MS 275], dacinostat [LAQ-824], belinostat [(PXD-101]), panobinostat [LBH589], mocetinostat [MGCD0103], CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g., valproic acid for epilepsy, may enroll after a 30-day washout period
• Patient has known hypersensitivity to the components of study drug or its analogs or paclitaxel
• NYHA Class III or IV congestive heart failure, myocardial infarction within the previous 6 months, QTc > 0.47 seconds, or uncontrolled arrhythmia
• Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study
• Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 5 years or are considered by their physician to be at less than 30% risk of relapse
• Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Shilpen Patel

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shilpen Patel

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2010-00715

Identifier Type: REGISTRY

Identifier Source: secondary_id

6600

Identifier Type: -

Identifier Source: org_study_id