NCT02149459

Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy

Improving the Response of Recurrent Glioma to Radiation Therapy Through Metabolic Intervention

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Sheba Medical Center · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Brain Neoplasms

Interventions

Type	Name	Description
RADIATION	Partial brain re-irradiation.	Partial brain re-irradiation to a dose of 30-35Gy delivered over 2 weeks (10 fractions).
DRUG	Metformin	Different cohorts will receive no, low dose or higher dose metformin.
BEHAVIORAL	low carbohydrate diet	Under close supervision of a dietician, patients will receive a low carbohydrate diet, enriched as necessary with medium chain triglyceride (MCT) supplements.

Timeline

• Start date: 2014-06-01
• Primary completion: 2018-07-01
• Completion: 2018-07-01
• First posted: 2014-05-29
• Last updated: 2017-10-27

Locations

1 site across 1 country: Israel