Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy
Status:
Unknown status
Trial end date:
2018-07-01
Target enrollment:
Participant gender:
Summary
Recurrent brain tumours are extremely aggressive and despite optimal treatment, median
survival is less than two years. One of the standard treatment options in this situation is
radiation therapy. Currently there is intense scientific interest concerning the abnormal
energy metabolism in cancer cells. All cells require energy in order to function, obtaining
'fuel' molecules such as glucose and fatty acids from the blood stream. Brain tumours exhibit
"metabolic reprogramming", meaning that their energy requirements and utilization of fuel
molecules are quite different from normal cells. Brain tumour cells are exquisitely dependant
on glucose as a source of energy. Animal studies have shown that when these tumours are
deprived of glucose they are very sensitive to radiation therapy.
In this clinical trial the investigators combine radiation therapy with a low-carbohydrate
diet, in patients with recurrent brain tumours. In addition, subjects will receive medication
with metformin, a drug usually used to treat diabetes. Metformin inhibits glucose metabolism
within cancer cells, and additionally has reported intrinsic anti-cancer activity. Subjects
will undergo advanced imaging and hormonal studies before, during and after the trial in
order to obtain maximal translational-scientific impact.
The hypothesis:
The metabolic changes induced by the combination of a moderately-low carbohydrate diet
combined with supplementary MCT and metformin therapy will selectively starve tumor cells.
While normal brain cells are capable of deriving energy from ketone bodies during glucose
restriction, tumor cells remain largely glucose-dependent for energy due to oncogene induced
down-regulation of oxidative phosphorylation. While the tumor cells are in this 'vulnerable'
state they will be less able to repair the damage induced by ionizing radiation.
Short-term implementation of the metabolic intervention (i.e. combined diet and metformin
therapy) prior to, during, and after hypofractionated (2 week) radiation therapy is expected
to increase tolerability, increase compliance and avoid the chronic metabolic complications
associated with extreme carbohydrate restriction diets.