NCT01281176

High-Dose or Low-Dose Vorinostat in Combination With Carboplatin or Paclitaxel in Treating Patients With Advanced Solid Tumors

Vorinostat and Carboplatin or Vorinostat and Paclitaxel in Patients With Advanced Solid Tumors: A Pharmacokinetic and Pharmacodynamic Study

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Adult Solid Neoplasm

Interventions

Type	Name	Description
DRUG	Carboplatin	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Paclitaxel	Given IV
OTHER	Pharmacological Study	Correlative studies
DRUG	Vorinostat	Given PO

Timeline

• Start date: 2011-02-09
• Primary completion: 2014-04-30
• Completion: 2026-04-17
• First posted: 2011-01-21
• Last updated: 2025-10-20

Locations

1 site across 1 country: United States