Vorinostat and Alvocidib in Treating Patients With Advanced Solid Tumors
|ClinicalTrials.gov Identifier: NCT00324480|
Recruitment Status : Completed
First Posted : May 11, 2006
Last Update Posted : February 24, 2014
|Condition or disease||Intervention/treatment||Phase|
|Unspecified Adult Solid Tumor, Protocol Specific||Drug: alvocidib Drug: vorinostat Other: pharmacological study||Phase 1|
I. Determine the maximum tolerated dose of vorinostat (SAHA) when given in combination with flavopiridol (alvocidib) in patients with advanced solid tumors.
II. Obtain preliminary data on the therapeutic activity of SAHA and flavopiridol in these patients.
III. Evaluate the role of p21, p53, and apoptotic markers relative to treatment response in patients treated with this regimen.
OUTLINE: This is a multicenter, open label, non-randomized, dose-escalation study of vorinostat (SAHA).
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib intravenously (IV) over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients are treated at the MTD of SAHA in combination with fixed-dose alvocidib. Once the MTD of SAHA in combination with fixed-dose alvocidib is determined, patients receive oral SAHA at one dose level below the MTD once daily on days 1-3 and 8-10 and divided-dose alvocidib IV over 30 minutes followed by alvocidib IV over 4 hours on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. If this schedule is well-tolerated, the MTD of SAHA in combination with divided-dose flavopiridol is determined as above. An additional 10 patients are treated at the MTD of SAHA in combination with divided-dose alvocidib. Patients undergo blood draws on days 1 and 9 of course 1 for pharmacokinetic analysis.
After completion of study treatment, patients are followed for 4 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With Flavopiridol in Advanced Solid Tumors|
|Study Start Date :||March 2006|
|Primary Completion Date :||April 2009|
Experimental: Treatment (chemotherapy, enzyme inhibitor)
Before beginning course 1 of study therapy, patients receive oral SAHA on days 1-3 in order to ensure tolerability of the drug. Beginning 1 week later, patients receive oral SAHA once daily on days 1-3 and 8-10 and fixed-dose alvocidib IV over 1 hour on days 2 and 9. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: vorinostat
Other Names:Other: pharmacological study
Other Name: pharmacological studies
- Maximum tolerated dose of vorinostat when administered in combination with a fixed dose of weekly flavopiridol [ Time Frame: Course 1 ]Defined as the dose one level below the dose at which two or more of the patients in the initial cohort experience dose limiting toxicities (DLT) during the first treatment course. Graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 Term.
- Clinical pharmacokinetics of vorinostat (SAHA) [ Time Frame: Week 1 of course 1 ]
- Therapeutic activity of SAHA and flavopiridol [ Time Frame: Not Provided ]
- Expression of p21, p53, and apoptotic markers relative to treatment response [ Time Frame: Baseline to 2 weeks after completion of study treatment ]Evaluated using immunohistochemistry.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00324480
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Gary Schwartz||Memorial Sloan Kettering Cancer Center|