A Phase I Dose Escalation to Maximally Tolerated Dose Trial of 5-Azacytidine (5 AC, NSC 102816) in Combination With Sodium Phenylbutyrate (PB, NSC 657802) in Patients With Refractory Solid Tumors
- Evaluate the safety and toxicity of azacitidine plus phenylbutyrate in patients with
refractory solid tumors.
- Determine the maximum tolerated dose of this treatment regimen where maximal gene
reexpression occurs in these patients.
- Evaluate the pharmacokinetics of these drugs in these patients.
- Determine the minimally effective dose of azacitidine in combination with
phenylbutyrate that elicits a biological or clinical response in these patients.
OUTLINE: This is a dose escalation study.
Patients receive azacitidine subcutaneously for 14-21 days and sodium phenylbutyrate IV
continuously for 1-7 days. Treatment repeats every 35 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses and durations of treatment with azacitidine
and phenylbutyrate 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 toxicities.
PROJECTED ACCRUAL: Approximately 3-50 patients will be accrued for this study within 12-18
Primary Purpose: Treatment
Michael A. Carducci, MD
Sidney Kimmel Comprehensive Cancer Center
United States: Federal Government
|Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins||Baltimore, Maryland 21231-2410|