Hydralazine as a Demethylating Agent in Rectal Cancer
This study will be conducted as a phase I/II clinical trial. In addition to determining the
maximum tolerated dose (MTD) of hydralazine, the phase I trial will be performed to identify
unexpected toxicities that may occur when hydralazine is used in conjunction with
neoadjuvant chemotherapy in normotensive patients with rectal cancer. Once the phase I
trial is successfully completed, the phase II trial to evaluate the efficacy of hydralazine
in producing a demethylation effect will begin.
This phase I/II trial will require between 31 to 47 patients to complete.
• Phase I Study
The objective of this study is to determine the MTD for Hydralazine added to standard
neoadjuvant chemotherapy for operable recta cancer. Four dose levels of hydralazine are
Dose Level 1: 150 mg/d 50 mg PO TID Dose Level 2: 200 mg/d 50 mg PO QID Dose Level 3:
225 mg/d 75 mg PO TID
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Health Services Research
The study design calls for an initial phase of dose-escalation in cohorts of 3 patients. There are no intra-patient changes in dose.
Ahmed M Safar, MD
University of Arkansas
United States: Institutional Review Board