Vorinostat, Paclitaxel, and Carboplatin in Treating Patients With Advanced or Refractory Solid Tumors
Summary
RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with paclitaxel and carboplatin may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of vorinostat when given together with paclitaxel and carboplatin in treating patients with advanced or refractory solid tumors.
Description
OBJECTIVES:
Primary
- Determine the recommended phase II dose of vorinostat (SAHA) when administered with paclitaxel and carboplatin in patients with advanced or refractory solid tumors.
Secondary
- Determine the dose-limiting toxicity (DLT) and other toxic effects of this regimen in these patients.
- Assess, preliminarily, evidence of antitumor activity of this regimen in these patients.
- Determine the pharmacokinetic parameters of this regimen in these patients.
- Determine the in vivo effects of this regimen in these patients.
OUTLINE: This is a multicenter, dose-escalation study of vorinostat (SAHA).
Patients receive oral SAHA once or twice daily on days 1-14* and paclitaxel IV over 3 hours followed by carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who have stable disease after the completion of 6 courses may receive single-agent SAHA at the discretion of the treating physician.
NOTE: *During the first treatment course only, patients receive SAHA on days -4 to 10.
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 3 or 2 of 6 patients experience DLT. An additional 6-12 patients are treated at the MTD.
After completion of study treatment, patients are followed at 1 month.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Study Design
Primary Purpose: Treatment
Conditions
Unspecified Adult Solid Tumor, Protocol Specific
Intervention
carboplatin, paclitaxel, vorinostat
Location
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh
Pennsylvania
United States
15232
Status
Completed
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00287937
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Nephroma, Mesoblastic
A solid, unencapsulated tumor of the KIDNEY composed of spindle mesenchymal cells that resemble FIBROBLASTS or muscle cells. The homogeneous mass typically extends into the renal parenchyma and replaces most of the kidney. In most cases, mesoblastic nephroma is benign and occurs in the fetus or newborn, and rarely in the older child or the adult.
Carcinoma, Ehrlich Tumor
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
Carboplatin
An organoplatinum compound that possesses antineoplastic activity.
Cystadenocarcinoma, Mucinous
A malignant cystic or semisolid tumor most often occurring in the ovary. Rarely, one is solid. This tumor may develop from a mucinous cystadenoma, or it may be malignant at the onset. The cysts are lined with tall columnar epithelial cells; in others, the epithelium consists of many layers of cells that have lost normal structure entirely. In the more undifferentiated tumors, one may see sheets and nests of tumor cells that have very little resemblance to the parent structure. (Hughes, Obstetric-Gynecologic Terminology, 1972, p184)
Mastocytoma
A solid tumor consisting of a dense infiltration of MAST CELLS. It is generally benign.
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