Dichloroacetate (DCA)

Phase 1, Open-Label, Single-Arm, Clinical and Metabolomic Study of Dichloroacetate (DCA) in Adults with Recurrent Malignant Brain Tumors

 
Location: University of Florida (USA)
Collaboration: Dr. Erin Dunbar, MD (principal investigator) & Dr. Peter Stacpoole, MD (co-investigator)

 

Malignant brain tumors are defined as any World Health Organization grade III-IV glioma and any solid tumor metastases to the brain. They share an increasing incidence, clinical and radiographic characteristics, pathobiology, paucity of effective therapies and prevalence of fatal outcomes. Thus, the international oncology community considers Phase I/II trials involving recurrent malignant brain tumors (RMBTs) scientifically valid and efficient for investigating promising agents. Importantly, RMBTs shared characteristics may be usefully exploited by an emerging class of pharmacological agents called “metabolic modulators” that exert their anti-tumor effects by causing fundamental changes in the manner in which tumors convert substrate fuels, such as glucose, into the energy that allow cancer cells to proliferate and metastasize.

Dichloroacetate (DCA) is the prototype for this new drug class and has been investigated clinically for decades, primarily at the University of Florida (UF) as an investigational drug for non-malignant metabolic diseases. Accordingly, a multidisciplinary research team at UF is conducting the first comprehensive study of DCA in adults with RMBTs, using a dose-escalation strategy. The primary goal is to determine the safety and tolerability of DCA in this patient population. Secondary goals include probative studies into the metabolism of DCA in these patients and to investigate the metabolic profile (“metabolome”) of RMBTs and the effects of DCA on them.
 

The study is ongoing, but not recruiting participants. Data currently obtained emphasize the importance of prior knowledge of GSTz1/MAAI genotype in assigning dosing regimens to patients participating in clinical trials of DCA.  Before accrual of a second cohort of patients the protocol has to be adapted to include this crucial characterization. As soon as IRB approval is obtained recruitment of patients for the second cohort will start .
The investigators are currently assimilation the findings from the initial cohort of patients for submitting a peer-reviewed publication this spring (2012).

More information about this study (NCT01111097) at www.clinicaltrials.gov.