Vorinostat, Paclitaxel, and Radiation Therapy in Treating... | NCT00662311

ID	Type	Description	Link
NCI-2010-00715	Registry Identifier	CTRP (Clinical Trial Reporting Program)

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Label	Type	Description	Intervention Names
Treatment (vorinostat with paclitaxel and radiotherapy)	Experimental	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 Drug: paclitaxel Radiation: radiation therapy

Name	Type	Description	Arm Group Labels	Other Names
vorinostat	Drug	Given PO	Treatment (vorinostat with paclitaxel and radiotherapy)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)	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.	8 weeks

Secondary Outcomes

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

Eligibility Module

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

Name	Affiliation	Role
Shilpen Patel	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium		Seattle	Washington	98109	United States

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Vorinostat 200 mg	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Vorinostat 200 mg	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
BG001	Vorinostat 300 mg	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
BG002	Vorinostat 400 mg	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
BG003	Total	Total of all reporting groups

Units	Counts
Participants	BG0005 BG0010 BG0020 BG0035

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

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.

Posted

Number

8 weeks

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Units	Counts
Participants	OG0005 OG0010 OG0020

Title

Denominators

Categories

Title	Measurements
	OG000NADue to adverse events we were unable to increase the vorinostat dosing beyond the first cohort of 200mg. The study was terminated prior to identifying the MTD.

Secondary

Radiological Response Rate as Assessed by CT

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

Posted

Count of Participants

Participants

12 weeks post-treatment, then every 3 months for 2 years, and then every 6 months for a year thereafter

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Secondary

Duration of Response

Posted

Median

Full Range

months

Up to 3 years

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Secondary

Progression-free Survival

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

Posted

Number

95% Confidence Interval

progression free survival probability

1 year

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Secondary

Overall Survival

Kaplan-Meier estimate

Posted

Number

95% Confidence Interval

survival probability

1 year

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Secondary

Safety and Toxicity of Vorinostat at the MTD as Assessed by NCI CTCAE Version 3.0

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.

Posted

Count of Participants

Participants

Weekly during treatment, 30 days post-treatment, and 12 weeks post-treatment

ID	Title	Description
OG000	Vorinostat 200 mg	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
OG001	Vorinostat 300 mg	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
OG002	Vorinostat 400 mg	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

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Vorinostat 200 mg	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	4	5	5
EG001	Vorinostat 300 mg	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	0	0	0
EG002	Vorinostat 400 mg	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	0	0	0

Serious Adverse Events

Term	Organ System	Statistical Information
Hyponatremia	Metabolism and nutrition disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
COPD Exacerbation	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Community Contacted Pneumonia	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Aspiration Pneumonia	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Radiation Pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Nausea	Gastrointestinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Fatigue	General disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk
Esophagitis	Gastrointestinal disorders	EG0001 affected5 at risk EG0010 affected0 at risk EG0020 affected0 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814	Aniline Compounds
D000588	Amines
D006877	Hydroxamic Acids
D006898	Hydroxylamines
D006880	Hydroxy Acids
D002264	Carboxylic Acids
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D004467	Economics
D004472	Health Care Economics and Organizations
D013812	Therapeutics
D055585	Physical Phenomena

ID	Term
D000077337	Vorinostat
D017239	Paclitaxel
D013660	Taxes
D011878	Radiotherapy
D011827	Radiation