This phase I clinical trial studies the side effects and the best dose of azacitidine and oxaliplatin in treating patients with advanced cancers that do not respond to treatment or have returned after any platinum therapy. Azacitidine is designed to activate (turn on) certain genes in cancer cells whose job is to fight tumors. Oxaliplatin is designed to block the growth and spread of new cancer cells, eventually destroying them, by damaging their deoxyribonucleic acid (DNA). Giving azacitidine with oxaliplatin may kill more cancer cells and may also reverse resistance to platinum-based drugs.
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of 5-azacytidine (azacitidine) and oxaliplatin combination regimen in patients with advanced solid tumors or lymphomas relapsed or refractory to any platinum compound. II. To define 5-azacytidine and oxaliplatin pharmacokinetics. SECONDARY OBJECTIVES: I. For patients treated in the expansion phase of this study: (a) to assess copper transport protein (CTR1) score; (b) to assess changes in global DNA methylation; and (c) to measure changes in oxaliplatin levels in tumor biopsies between pretreatment and day 12 of the first cycle of 5-azacytidine plus oxaliplatin therapy. II. To correlate results of the pharmacokinetic studies of 5-azacytidine and oxaliplatin with changes in CTR1, changes in global DNA methylation and changes in oxaliplatin levels in tissue biopsies of patients treated in the expansion phase of this study. OUTLINE: This is a dose-escalation study. Patients receive azacitidine IV over 15-30 minutes on days 1-5 and oxaliplatin IV over 2 hours on days 2-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
M D Anderson Cancer Center
Houston, Texas, United States
MTD graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time frame: 28 days
Changes in concentration of oxaliplatin
Time frame: Baseline to day 12
Changes in DNA methylation
Time frame: Baseline to day 12
Changes in the CTR1 score
Time frame: Baseline to day 28
Pharmacokinetic parameters of azacitidine and oxaliplatin
Compartmental and non-compartmental modeling will be used to derive pharmacokinetic parameters, including maximum concentration (Cmax), time to maximum plasma concentration (Tmax), area under the curve (AUC), t ½ alpha (a), t ½ beta (B), volume of distribution (Vd), and clearance.
Time frame: Days 1 and 5 of course 1 (azacitidine) and day 2 of course 1 (oxaliplatin)
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