This phase I trial is studying the side effects and best dose of decitabine in treating patients with metastatic or unresectable refractory solid tumors or lymphomas. Drugs used in chemotherapy, such as decitabine, work in different ways to stop cancer cells from dividing so they stop growing or die
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of single agent decitabine and its toxicity using this schedule in this population of patients with solid tumors or lymphomas. II. Definition of the dose at which tumor DNA demethylation is optimum. III. Definition of the dose at which peripheral blood mononuclear cell (PBMN) demethylation is optimal. IV. Definition of decitabine pharmacokinetics and correlation of plasma concentrations with hypomethylation effects. SECONDARY OBJECTIVES: I. Preliminary assessment of decitabine efficacy (objective response). OUTLINE: This is a dose-escalation study. Patients receive decitabine IV over 1 hour on days 1-5 or on days 1-5 and 8-12. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of decitabine 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
M D Anderson Cancer Center
Houston, Texas, United States
Phase II dose will be defined as the lowest dose at or below the maximum tolerated dose (MTD; based on dose limiting toxicity) consistent with a plateau reduction in DNA methylation in target tumor tissue
Time frame: 4 weeks
Tumor demethylation response, measured by percent change in DNA methylation using the ALU assay
Analysis of variance with Fisher's protected least significant difference to group dose levels that elicit consistent demethylation response will be used.
Time frame: Baseline to day 12 course 1
Adequacy of peripheral blood mononuclear cell DNA methylation as a surrogate for tumor DNA methylation, measured by effect of dose on reduction in DNA methylation in peripheral blood mononuclear cells
Time frame: Day 12 course 1
Pharmacokinetic parameters, including Cmax, Tmax, AUC, t ½ α, t ½ β, Vd, and clearance
Time frame: Days 1 and 5 of course 1
Response using RECIST
Time frame: Up to 4 years
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