The Safety and Efficacy of DCA for the Treatment of Brain Cancer
Status:
Completed
Trial end date:
2009-08-01
Target enrollment:
Participant gender:
Summary
Malignant gliomas, which include Glioblastoma multiforme (GBM), are the most common and most
aggressive types of brain cancer, accounting for approximately 60% of primary brain tumors.
These tumors are characterized by diverse molecular abnormalities (within the same tumor),
which, along with the difficulties of many standard chemotherapies crossing the blood
barrier, contribute to the very poor response to therapy and poor survival.
We recently showed that Dichloroacetate (DCA, an inhibitor of the mitochondrial pyruvate
dehydrogenase kinase) was able to depolarize cancer (but not normal) mitochondria and induce
apoptosis in cancer but not normal tissues. We believe that altering the metabolism of
cancers like glioblastoma (DCA switches metabolism from the cytoplasmic glycolysis to the
mitochondrial glucose oxidation) we inhibit the resistance to apoptosis that characterizes
cancer. Because metabolism (i.e. glycolysis) is the end result of many and diverse molecular
pathways, the effects of DCA might be positive in cancers with diverse molecular backgrounds.
DCA is also a very small molecule that readily crosses the blood brain barrier. Therefore we
hypothesize that DCA will be an effective and relative non-toxic potential therapy for
malignant gliomas.
We are conducting a phase II trial with 2 parallel arms: a) patients with newly diagnosed
malignant gliomas and b) patients with recurrent gliomas or gliomas that have failed standard
therapy (which includes surgery, radiotherapy and chemotherapy). All patients need to have a
histological diagnosis. DCA will be given orally and patients will be followed for a minimum
of 6 months. The tumor size will be followed by standard MRI or CT criteria and glucose
uptake (a direct effect of DCA on the tumor) will be measured by FDG-PET imaging. Several
clinical parameters and quality of life will be followed. Potential toxicity (particularly
peripheral neuropathy) will be closely followed and dose-de-escalation protocols are in place
in case of toxicity. In addition, escape protocols for the application of standard therapy
(when appropriate) are in place in patients with no evidence of response to DCA. In vitro
studies will be performed in the tissues obtained at the time of surgery (where appropriate)
and correlated prospectively with clinical data.
There is limited ability to accept patients outside of Alberta; this is in part because the
visit and testing schedule is intense, requiring residence in Edmonton for at least 6 months.