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

• Sponsor: University of Washington (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00662311
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 5
• Location: 1
• Arm: 1
• Duration (Months): 42
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer	Drug: vorinostat; Drug: paclitaxel; Radiation: radiation therapy	Phase 1/Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

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

2. 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.

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Clinical Trial Evaluating the Use of Vorinostat Combined With Paclitaxel and Radiotherapy in Patients With Inoperable Stage III Non-Small Cell Lung Cancer Unable to Tolerate Cisplatin
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: vorinostat; Given PO; Other Names: L-001079038 SAHA suberoylanilide hydroxamic acid Zolinza ; Drug: paclitaxel; Given IV; Other Names: Anzatax Asotax TAX Taxol ; Radiation: radiation therapy; Undergo radiation therapy; Other Names: irradiation radiotherapy therapy, radiation

Outcome Measures

Primary Outcome Measures

1. MTD of Vorinostat When Administered in Combination With Paclitaxel and Radiotherapy Therapy as Assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I) [8 weeks]

   Defined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted > 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade > 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.

Secondary Outcome Measures

1. Radiological Response Rate as Assessed by CT [12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafter]

   Count of participants with stable disease or partial response. Patients were evaluated for treatment response per RECIST criteria (version 1.0).

2. Duration of Response [Up to 3 years]

3. Progression-free Survival [1 year]

   Kaplan-Meier estimate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).

4. Overall Survival [1 year]

   Kaplan-Meier estimate

5. Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0 [Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatment]

   Count of participants with a grade 3 or higher toxicity. Toxicities were assessed using the NCI CTCAE (v3.0). Grade 3 or higher toxicities were considered worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Shilpen Patel, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shilpen Patel, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT00662311
• Other Study ID Numbers: 6600; NCI-2010-00715
• First Posted: Apr 21, 2008
• Last Update Posted: Jun 14, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Vorinostat

Study Results

Participant Flow

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Period Title: Overall Study
STARTED	5	0	0
COMPLETED	4	0	0
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg	Total
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Total of all reporting groups
Overall Participants	5	0	0	5
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	77	77
Sex: Female, Male (Count of Participants)
Female	3 60%	3 Infinity
Male	2 40%	2 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	5 100%	5 Infinity
Unknown or Not Reported	0 0%	0 NaN

Outcome Measures

1. Primary Outcome

Title	MTD of Vorinostat When Administered in Combination With Paclitaxel and Radiotherapy Therapy as Assessed by NCI Common Toxicity Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)
Description	Defined as the highest dose level at which no more than 1 of 6 patients experiences dose-limiting toxicity (DLT). Toxicity was graded according to the National Institutes of Health Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. A DLT was defined as any Grade 3 or higher non-hematologic adverse event with the exception of alopecia, fatigue, or anorexia. Nausea and/or vomiting that persisted > 48 hours despite optimal medical management at grade 3 or higher was considered a DLT. Hematologic dose-limiting toxicity was defined as either: Grade 4 neutropenia lasting for ≥ 7 days in duration, Grade > 3 febrile neutropenia with/without infection, Grade 4 thrombocytopenia or Grade 5 hematologic toxicity.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	5	0	0
Number [mg]	NA

2. Secondary Outcome

Title	Radiological Response Rate as Assessed by CT
Description	Count of participants with stable disease or partial response. Patients were evaluated for treatment response per RECIST criteria (version 1.0).
Time Frame	12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafter

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	5	0	0
12 Weeks	4 80%
6 Months	3 60%
9 Months	3 60%
12 Months	1 20%
15 Months	1 20%
18 Months	1 20%
21 Months	1 20%
24 Months	1 20%
27 Months	1 20%
33 Months	0 0%
39 Months	0 0%

3. Secondary Outcome

Title	Duration of Response
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	4	0	0
Median (Full Range) [months]	10

4. Secondary Outcome

Title	Progression-free Survival
Description	Kaplan-Meier estimate. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	5	0	0
Number (95% Confidence Interval) [progression free survival probability]	0.20

5. Secondary Outcome

Title	Overall Survival
Description	Kaplan-Meier estimate
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	5	0	0
Number (95% Confidence Interval) [survival probability]	0.60

6. Secondary Outcome

Title	Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0
Description	Count of participants with a grade 3 or higher toxicity. Toxicities were assessed using the NCI CTCAE (v3.0). Grade 3 or higher toxicities were considered worse.
Time Frame	Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat 200 mg	Vorinostat 300 mg	Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy	Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
Measure Participants	5	0	0
Count of Participants [Participants]	4 80%

Adverse Events

Arm/Group Title	Vorinostat 200 mg		Vorinostat 300 mg		Vorinostat 400 mg
Arm/Group Description	Cohort 1: Patients receive 200 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy		Cohort 2: Patients receive 300 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy		Cohort 3: Patients receive 400 mg 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. vorinostat: Given PO paclitaxel: Given IV radiation therapy: Undergo radiation therapy
All Cause Mortality
	Vorinostat 200 mg		Vorinostat 300 mg		Vorinostat 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Vorinostat 200 mg		Vorinostat 300 mg		Vorinostat 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		0/0 (NaN)		0/0 (NaN)
Gastrointestinal disorders
Nausea	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Esophagitis	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
General disorders
Fatigue	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Metabolism and nutrition disorders
Hyponatremia	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Respiratory, thoracic and mediastinal disorders
COPD Exacerbation	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Community Contacted Pneumonia	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Aspiration Pneumonia	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Pulmonary Embolism	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Radiation Pneumonitis	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Dyspnea	1/5 (20%)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Vorinostat 200 mg		Vorinostat 300 mg		Vorinostat 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.