NCT00084981

Decitabine and Valproic Acid in Treating Patients With Non-Small Cell Lung Cancer

A Phase I Study of Decitabine in Combination With Valproic Acid in Patients With Non-Small Cell Lung Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (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 decitabine and valproic acid in treating patients with non-small cell lung cancer. Drugs used in chemotherapy, such as decitabine and valproic acid, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of decitabine and valproic acid in patients with non-small cell lung cancer. II. Determine the recommended phase II dose of this regimen in these patients. SECONDARY OBJECTIVES: I. Determine the ability of this regimen to lead to biological changes in tumor and surrogate tissues in these patients, including hypomethylation of target genes known to be methylated in NSCLC (CDKN2, APC, BMP3B, CDH1 and RASSF1A) in biopsy specimens and surrogate tissues (peripheral blood mononuclear cells \[PBMC\] and plasma/serum DNA); acetylation and methylation changes in histones from tumor and surrogate tissues (PBMC and oral epithelial cells); inhibition of histone deacetylase (HDAC) activity in peripheral blood; pharmacokinetic analysis of Decitabine and Valproic Acid; DNA methyltransferase 1 (DNMT1) protein loss in PBMC and buccal cells; response of hemoglobin F in patients with non-hematologic conditions to DNMT and HDAC inhibition; and preliminary evidence of antitumor activity in non-small cell lung cancer. OUTLINE: This is a dose-escalation study. Patients receive decitabine IV over 1 hour on days 1-10 and oral valproic acid three times daily on days 5-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of decitabine and valproic acid 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. After the MTD is determined, an additional 6 patients are treated at that dose.

Conditions

• Recurrent Non-small Cell Lung Cancer
• Stage IV Non-small Cell Lung Cancer

Interventions

Type	Name	Description
DRUG	decitabine	Given IV
DRUG	valproic acid	Given PO
OTHER	pharmacological study	Correlative studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2004-04-01
• Primary completion: 2013-02-01
• First posted: 2004-06-11
• Last updated: 2013-09-30

Locations

1 site across 1 country: United States