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Treatment of Recurrent Brain Tumors: Metabolic Manipulation Combined With Radiotherapy

NCT02149459 · Status: UNKNOWN · Phase: PHASE1 · Type: INTERVENTIONAL · Enrollment: 18

Last updated 2017-10-27

No results posted yet for this study

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

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.

Sponsors & Collaborators

  • European Union

    collaborator OTHER

  • Sheba Medical Center

    lead OTHER_GOV

Principal Investigators

  • Yaacov R Lawrence, MA MBBS MRCP · Sheba Medical Center

Study Design

Allocation
NA
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-06-30
Primary Completion
2018-07-31
Completion
2018-07-31

Countries

  • Israel

Study Locations

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Entities

Drugs
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02149459 on ClinicalTrials.gov