The trials will test the synergistic effect of the combination therapy in the treatment of patients with advanced myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML).
HDAC inhibitors, such as MGCD0103, and demethylating agents such as Vidaza both act by turning on tumor suppressor genes that have been inappropriately turned off. Tumor suppressor genes are the body’s natural defense against cancer. Preclinical studies demonstrate that MGCD0103 and demethylating agents synergistically kill cancer cells.
In the phase I portion of the trial, MGCD0103 will be given orally, three times per week in combination with standard Vidaza treatment. Key objectives of this portion of the study will be to evaluate the compatibility and safety of administering these two agents together, and to determine the maximum dose of MGCD0103 that can safely be administered in this combination.
Secondary objectives include determining the dose-limiting toxicities, the objective responses to MGCD0103 and Vidaza, and measuring the pharmacodynamic and pharmacokinetic effects.
In the phase II portion of the trial, the purpose will be to determine the overall response rate. The trial is expected to enroll up to 50 patients at five sites at leading cancer centers in North America.
“We are pleased with our MGCD0103 phase I results in hematological cancers and believe that using Vidaza in combination with MGCD0103 will enhance our ability to target cancers such as MDS and AML,” said Dr Robert Martell, vice president and chief medical officer of MethylGene.