Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy (SMC 0712-13)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02149459|
Recruitment Status : Recruiting
First Posted : May 29, 2014
Last Update Posted : October 27, 2017
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 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.
|Condition or disease||Intervention/treatment||Phase|
|Brain Neoplasms||Radiation: Partial brain re-irradiation. Drug: Metformin Behavioral: low carbohydrate diet||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Improving the Response of Recurrent Glioma to Radiation Therapy Through Metabolic Intervention|
|Study Start Date :||June 2014|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||July 2018|
Experimental: treatment arm
Partial brain re-irradiation combined with metabolic intervention (low carbohydrate diet and/or metformin treatment)
Radiation: Partial brain re-irradiation.
Partial brain re-irradiation to a dose of 30-35Gy delivered over 2 weeks (10 fractions).
Other Names:Drug: Metformin
Different cohorts will receive no, low dose or higher dose metformin.
Other Names: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.
- Number of patients with adverse events. [ Time Frame: 8 weeks ]The investigators will track adverse events in order to determine the safety of the intervention.
- Number of patients completing the trial. [ Time Frame: 8 weeks ]We will track patient compliance in order to determine the tolerability of the intervention.
- Number of patients whose brain tumors respond on imaging. [ Time Frame: 8 weeks ]
- Number of patients who demonstrate changes in systemic energy metabolism. [ Time Frame: 8 weeks ]We will assess plasma levels of glucose, insulin and other relevant hormones before, during and after the intervention.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02149459
|Contact: Yaacov R Lawrence, MBBS MA MRCPemail@example.com|
|Contact: Hila Gnessin, Bsc||972-3-530-7340||Hila.Gnessin@sheba.health.gov.il|
|Sheba Medical Center||Recruiting|
|Ramat Gan, Israel, 52621|
|Principal Investigator:||Yaacov R Lawrence, MA MBBS MRCP||Sheba Medical Center|