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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The primary aim is to study the effects of vorinostat on cyclin E, cyclin D1 and Ki-67 expression in aerodigestive tract tumors (lung, esophagus, and head and neck). Secondary aims are: To evaluate the concentration of vorinostat in tumor tissue and to correlate tumor tissue distribution with the plasma level in these patients; to perform exploratory analyses of the effects of vorinostat on the induction of apoptosis or necrosis in treated as compared to untreated tumors and on expression of p21, p27, EGFR and phospho-EGFR in aerodigestive tract tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vorinostat 400 mg | Experimental | Vorinostat will be administered orally once daily in an open-labeled unblinded manner to all subjects enrolled in the study. Subjects will received 400 mg once daily on a continuous daily basis for 7 to 10 days prior to surgical resection. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vorinostat | Drug | Vorinostat will be administered orally once daily in an open-labeled, unblinded manner to all subjects enrolled in the study. Subjects will receive vorinostat 400 mg once daily on a continuous daily basis for 7 to 10 days prior to surgical resection. Vorinostat should be taken with food within 0 to 30 minutes of a meal if possible. Patients should take the medication at approximately the same time each day on an ongoing basis. Missed doses will not be made up. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Tumor Markers on Tumors of the Lung, Esophagus, or Head and Neck, After 7 Days of Treatment With Vorinostat | Immunohistochemical score, defined as: 0, no tumor cells staining positive; 1+, 0% to 50% of tumor cells staining positive; 2+, 50% to 75% of tumor cells staining positive; and 3+, 75% to 100% of tumor cells staining positive. The change in the score before and after treatment is percentage - 0-100 | Baseline to Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Concentration of Vorinostat in Tumor Tissue | Concentration of vorinostat in tumor tissue will be measured after 7 days of use of Vorinostat. | Day 7 from Baseline |
| Effects of Vorinostat Treatment on Induction of Apoptosis or Necrosis in Treated vs. Untreated Tumors |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Konstantin H. Dragnev, MD | Dartmouth-Hitchcock Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
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Patients with clinical Stage I, II, III A NSCLC or Stage I, II , III esophageal cancer or Stage I, II, III, IV A Head and Neck cancer and a pre-treatment biopsy having at least 3 unstained slides were eligible. Patients were recruited from the oncology clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Vorinostat | Vorinostat 400mg one daily administered orally for 7 to 10 days prior to a second biopsy/ thoracotomy. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Vorinostat | Vorinostat group |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 | Changes in Tumor Markers on Tumors of the Lung, Esophagus, or Head and Neck, After 7 Days of Treatment With Vorinostat | Immunohistochemical score, defined as: 0, no tumor cells staining positive; 1+, 0% to 50% of tumor cells staining positive; 2+, 50% to 75% of tumor cells staining positive; and 3+, 75% to 100% of tumor cells staining positive. The change in the score before and after treatment is percentage - 0-100 | Participants who had at least two days days of treatment with vorinostat. | Posted | Median | 95% Confidence Interval | percentage of change | Baseline to Day 7 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Vorinostat | Vorinostat group |
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Patients were asked to take vorinostat for at least 7 days with a maximum of 10 days. Two participants did not follow directions correctly and took the pills for 3 days and 2 days. One participant took medication at 100mg per day and not the 400 mg
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Konstnatin Dragnev, MD Professor of Medicine | Dartmouth-Hitchcock Medical Center | 603-650-6344 | Konstantin.H.Dragnev@Hitchcock.org |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D004938 | Esophageal Neoplasms |
| D006258 | Head and Neck Neoplasms |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077337 | Vorinostat |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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|
vorinostat's effects on induction of apoptosis or necrosis in treated vs untreated tumors and on p21, p27, EGFR, and phospho-EGFR expression aerodigestive tract tumors. Immunohistochemical score is defined as follows: 0, no tumor cells staining positive; 1+, 0% to 50% of tumor cells staining positive; 2+, 50% to 75% of tumor cells staining positive; and 3+, 75% to 100% of tumor cells staining positive. |
| Baseline to day 7 |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Units | Counts |
|---|
| Participants |
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| Secondary | Concentration of Vorinostat in Tumor Tissue | Concentration of vorinostat in tumor tissue will be measured after 7 days of use of Vorinostat. | Posted | Median | 95% Confidence Interval | ng/mg | Day 7 from Baseline |
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| Secondary | Effects of Vorinostat Treatment on Induction of Apoptosis or Necrosis in Treated vs. Untreated Tumors | vorinostat's effects on induction of apoptosis or necrosis in treated vs untreated tumors and on p21, p27, EGFR, and phospho-EGFR expression aerodigestive tract tumors. Immunohistochemical score is defined as follows: 0, no tumor cells staining positive; 1+, 0% to 50% of tumor cells staining positive; 2+, 50% to 75% of tumor cells staining positive; and 3+, 75% to 100% of tumor cells staining positive. | Posted | Mean | 95% Confidence Interval | score on a scale | Baseline to day 7 |
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| 0 |
| 10 |
| 0 |
| 10 |
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| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D000588 |
| Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |