NCT00331955

Vorinostat and Doxorubicin in Treating Patients With Metastatic or Locally Advanced Solid Tumors

Phase I Trial of Vorinostat (NSC-701852, Suberoylanilide Hydroxamic Acid) and Doxorubicin (NSC-123127, Adriamycin)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial is studying the side effects and best dose of vorinostat when given together with doxorubicin in treating patients with metastatic or locally 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 doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may help doxorubicin work better by making tumor cells more sensitive to the drug.

Detailed description

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of vorinostat (SAHA) and doxorubicin hydrochloride in patients with metastatic or locally advanced solid tumors. II. Determine the maximum tolerated dose of vorinostat when administered with doxorubicin hydrochloride in patients treated with this regimen. SECONDARY OBJECTIVES: I. Determine the response rate (complete response \[CR\] and partial response \[PR\]) and clinical benefits rate (CR, PR, and stable disease \> 12 weeks) in patients treated with this regimen. II. Determine the pharmacokinetics and pharmacodynamics of vorinostat and doxorubicin hydrochloride and their interaction. III. Determine the effects of vorinostat on histone acetylation in peripheral blood mononuclear cells and tumors. IV. Determine the effects of vorinostat on DNA damage induced by doxorubicin hydrochloride as a function of topoisomerase II expression. V. Determine the effects of vorinostat on genes and proteins crucial for the maintenance of chromatin structure. OUTLINE: This is a non-randomized, open-label, dose-escalation study of vorinostat. Patients receive oral vorinostat twice daily for 5 doses on days 1-3, 8-10, and 15-17 and doxorubicin hydrochloride IV on days 3, 10, and 17. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responding or stable disease after 6 courses of treatment may continue to receive vorinostat alone in the absence of disease progression. Cohorts of 3-6 patients receive escalating doses of vorinostat 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 dose-limiting toxicity. Up to15 patients are treated at the MTD. Mandatory biopsies are required in these patients. Patients undergo blood collection and tumor biopsies periodically during the study for pharmacologic, pharmacokinetic, pharmacodynamic, and biomarker correlative studies. After completion of study treatment, patients are followed for at least 30 days. PROJECTED ACCRUAL: A total of 40 patients will be accrued to this study.

Conditions

• Unspecified Adult Solid Tumor, Protocol Specific

Interventions

Type	Name	Description
DRUG	doxorubicin hydrochloride	Given IV
DRUG	vorinostat	Given orally
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2006-03-01
• Primary completion: 2012-06-01
• First posted: 2006-05-31
• Last updated: 2013-07-02

Locations

1 site across 1 country: United States