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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2011-02575 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| CDR0000693736 | |||
| UCCRC-10-652-B | |||
| 10-652-B | Other Identifier | University of Chicago Comprehensive Cancer Center | |
| 8844 | Other Identifier | CTEP | |
| P30CA014599 | U.S. NIH Grant/Contract | View source | |
| U01CA069852 | U.S. NIH Grant/Contract | View source |
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This randomized pilot clinical trial studies high-dose or low-dose vorinostat in combination with carboplatin or paclitaxel in treating patients with advanced solid tumors. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving different doses of vorinostat together with carboplatin or paclitaxel may kill more tumor cells.
PRIMARY OBJECTIVES:
I. To determine whether high dose, short course vorinostat achieves higher peak serum concentrations than standard dosing.
SECONDARY OBJECTIVES:
I. To determine the toxicity profiles of two different escalated intermittent dosing schedules of vorinostat combined with carboplatin at an area under curve (AUC) of 5.
II. To describe the response rate in patients with advanced solid tumors treated with these regimens.
III. To develop pharmacodynamic markers for vorinostat. IV. To determine the toxicity profiles of escalated intermittent dosing schedule of vorinostat at 1200 mg combined with paclitaxel at 175 mg/m^2 and to describe the response rate in patients with advanced solid tumors treated with this regimen.
OUTLINE: Patients are randomized to 1 of 4 treatment arms.
ARM I: Patients receive high-dose vorinostat orally (PO) once daily (QD) on days 1-3 and low-dose vorinostat PO QD on days 8-10 (course 1). After 5 days, patients receive high-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent courses.
ARM II: Patients receive high-dose vorinostat and low-dose vorinostat as in arm I. After 5 days, patients receive lower-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent courses.
ARM III: Patients receive low-dose vorinostat PO QD on days 1-3 and high-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and carboplatin as in Arm I.
ARM IV: Patients receive low-dose vorinostat and high-dose vorinostat as in Arm III. After 5 days, patients receive vorinostat and carboplatin as in Arm II.
ARM V: Patients receive low-dose vorinostat PO QD on days 1-3 and mid-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive mid-dose vorinostat PO QD on days 1-3 and paclitaxel IV over 3 hours on day 3.
ARM VI: Patients receive mid-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and paclitaxel as in Arm V.
In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for 4 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm I (high- and low-dose vorinostat and carboplatin) | Experimental | Patients receive high-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive high-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3 of all subsequent courses. |
|
| Arm II (high- and low-dose vorinostat and carboplatin) | Experimental | Patients receive high-dose vorinostat and low-dose vorinostat as in Arm I. After 5 days, patients receive lower-dose vorinostat PO QD on days 1-3 and carboplatin IV over 30 minutes on day 3. |
|
| Arm III (low- and high-dose vorinostat and carboplatin) | Experimental | Patients receive low-dose vorinostat PO QD on days 1-3 and high-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive vorinostat and carboplatin as in Arm I. |
|
| Arm IV (low- and high-dose vorinostat and carboplatin) | Experimental | Patients receive low-dose vorinostat and high-dose vorinostat as in Arm III. After 5 days, patients receive vorinostat and carboplatin as in Arm II. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Carboplatin | Drug | Given IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Peak concentrations (Cmax) of vorinostat at 400, 1200, and 1600 mg | 0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events of two different escalated intermittent dosing schedules of vorinostat combined with carboplatin as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 | The percentage of patients with any grade and with grade 3 or higher toxicity will be reported along with 95% confidence intervals. | Up to 4 weeks |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael L Maitland | University of Chicago Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Comprehensive Cancer Center | Chicago | Illinois | 60637 | United States |
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| Arm V (low- and mid-dose vorinostat and paclitaxel) | Experimental | Patients receive low-dose vorinostat PO QD on days 1-3 and mid-dose vorinostat PO QD on days 8-10 (course 0). After 5 days, patients receive mid-dose vorinostat PO QD on days 1-3 and paclitaxel IV over 3 hours on day 3. |
|
| Arm VI (mid- and low-dose vorinostat and paclitaxel) | Experimental | Patients receive mid-dose vorinostat PO QD on days 1-3 and low-dose vorinostat PO QD on days 8-10. After 5 days, patients receive vorinostat and paclitaxel as in Arm V. |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Paclitaxel | Drug | Given IV |
|
|
| Pharmacological Study | Other | Correlative studies |
|
| Vorinostat | Drug | Given PO |
|
|
| Pharmacodynamic markers of vorinostat activity, including AUC and changes in platelet counts | The correlation between changes in AUC and changes in platelet counts will be analyzed by a non-parametric Spearman's correlation coefficient with 95% confidence intervals. Similar analyses will be performed for Cmax and other pharmacodynamic markers. The association between genetic polymorphisms and vorinostat pharmacokinetics analyzed using analysis of variance. | 0 (pre-treatment), 60, 120, 180, 240, 360 and 480 minutes and 24 hours after vorinostat administration on days 3 and 10 of course 0 and on day 3 of course 1 |
| ID | Term |
|---|---|
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| D013660 | Taxes |
| D000077337 | Vorinostat |
| ID | Term |
|---|---|
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| 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 |
| D000813 | Anilides |
| D000577 | Amides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
| D006877 | Hydroxamic Acids |
| D006898 | Hydroxylamines |
| D006880 | Hydroxy Acids |
| D002264 | Carboxylic Acids |
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