Recurrent Glioblastoma
Conditions
Keywords
ketogenic diet, glioma, fasting, reirradiation, nutrition
Brief summary
Increased glucose metabolism is characteristic for solid tumors. Thereby, glucose is important for the generation of ATP, supply of anabolic substrates and defense against reactive oxygen species in tumor cells. In preclinical models, restricting glucose availability using a ketogenic diet, calorie-restriction or transient fasting inhibits tumor growth. Therefore, the purpose of the study is to evaluate whether a calorie-restricted, ketogenic diet and transient fasting can enhance the efficacy of reirradiation in patients with recurrent glioblastoma.
Interventions
DIETARY_SUPPLEMENTcalorie-restricted ketogenic diet and transient fasting
On day 1-3 and day 7-9, restriction of carbohydrates to \< 60 g and of calories to 21-23 kcal/kg per day, on day 4-6 fasting. On day 1-3 and 7-9, restriction of carbohydrates can be supported by the use of drinks provided by Tavarlin.
DIETARY_SUPPLEMENTstandard nutrition
nutrition as recommended by the german society for nutrition, 30 kcal/kg per day
Sponsors
Tavarlin
Johann Wolfgang Goethe University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age \>= 18 years * recurrence of a histologically confirmed glioblastoma or gliosarcoma * at least 6 months after first surgery * at least 6 months after first radiotherapy * interdisciplinary recommendation for reirradiation * karnofsky performance status \>= 60, ECOG \<= 2 * creatinine \<= 2,0 mg/dl, urea \<= 100 mg/dl * ALAT, ASAT \<= 7x upper normal limit
Exclusion criteria
* bowel obstruction, subileus * insulin-dependent diabetes * decompensated heart failure (NYHA \> 2) * myocardial infarction within the last 6 months, symptomatic atrial fibrillation * severe acute infection * malnutrition, cachexia * other medical conditions that might increase the risk of the dietary intervention * pregnancy * uncontrolled thyroid function * pancreatic insufficiency * dementia or other clinically relevant alterations of the mental status which could impair the ability of the patient to apply to the diet or understand the informed consent of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free-survival | 6 months | Progression-free-survival rates 6 months after reirradiation based on response assessment in neuro-oncology criteria (RANO) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability as Defined as Number of Patients With Adverse Events | day 1-12 | Safety and tolerability of the calorie-restricted, ketogenic diet and the transient fasting as defined as number of patients with adverse events |
| Progression-free-survival | 1 month, 3 months | progression-free-survival rates 1 month and 3 month after reirradiation |
| Overall Survival | 12 months | overall survival after the reirradiation |
| Frequency of Seizures | day 1-12 | frequency of seizures at day 1-12 |
| Feasibility Measured as Median Number of Days on Diet Per Patient and Average Calorie and Carbohydrate Intake Per Day During Day 1-9 | day 1-12 | Feasibility of the calorie-restricted, ketogenic diet and the transient fasting measured as median number of days on diet per patient and average calorie and carbohydrate intake per day during day 1-9 |
| Quality of Life as Measured by the EORTC Quality of Life Questionnaire | day 1-12 | Quality of life at day 1-12 as measured by the EORTC Quality of Life Questionnaire |
| Depression | day 1-12 | depression as measured by SCL-90 at day 1-12 |
| Attention | day 1-12 | attention as measured by d2-testing at day 1-12 |
| Response | 1 month | response assessment 1 month after reirradiation |
| Ketosis | day 1-12 | urine and blood ketosis and metabolic parameters (glucose, insulin, IGF-1) during day 1-12 |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketogenic Diet and Transient Fasting Calorie-restricted, ketogenic diet and transient fasting during reirradiation
calorie-restricted ketogenic diet and transient fasting: On day 1-3 and day 7-9, restriction of carbohydrates to \< 60 g and of calories to 21-23 kcal/kg per day, on day 4-6 fasting. On day 1-3 and 7-9, restriction of carbohydrates can be supported by the use of drinks provided by Tavarlin. | 25 |
| Standard Nutrition nutrition according to recommendations of the German society for nutrition during reirradiation
standard nutrition: nutrition as recommended by the german society for nutrition, 30 kcal/kg per day | 25 |
| Total | 50 |
Baseline characteristics
| Characteristic | Ketogenic Diet and Transient Fasting | Total | Standard Nutrition |
|---|---|---|---|
| Age, Continuous | 56 years | 57 years | 58 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 50 Participants | 25 Participants |
| Region of Enrollment Germany | 25 participants | 50 participants | 25 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 20 Participants | 38 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 22 |
| other Total, other adverse events | 4 / 20 | 5 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 22 |
Outcome results
Primary
Progression-free-survival
Progression-free-survival rates 6 months after reirradiation based on response assessment in neuro-oncology criteria (RANO)
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketogenic Diet and Transient Fasting | Progression-free-survival | 20 percentage of participants |
| Standard Nutrition | Progression-free-survival | 16 percentage of participants |
Secondary
Attention
attention as measured by d2-testing at day 1-12
Time frame: day 1-12
Secondary
Depression
depression as measured by SCL-90 at day 1-12
Time frame: day 1-12
Secondary
Feasibility Measured as Median Number of Days on Diet Per Patient and Average Calorie and Carbohydrate Intake Per Day During Day 1-9
Feasibility of the calorie-restricted, ketogenic diet and the transient fasting measured as median number of days on diet per patient and average calorie and carbohydrate intake per day during day 1-9
Time frame: day 1-12
Secondary
Frequency of Seizures
frequency of seizures at day 1-12
Time frame: day 1-12
Secondary
Ketosis
urine and blood ketosis and metabolic parameters (glucose, insulin, IGF-1) during day 1-12
Time frame: day 1-12
Secondary
Overall Survival
overall survival after the reirradiation
Time frame: 12 months
Secondary
Progression-free-survival
progression-free-survival rates 1 month and 3 month after reirradiation
Time frame: 1 month, 3 months
Secondary
Quality of Life as Measured by the EORTC Quality of Life Questionnaire
Quality of life at day 1-12 as measured by the EORTC Quality of Life Questionnaire
Time frame: day 1-12
Secondary
Response
response assessment 1 month after reirradiation
Time frame: 1 month
Secondary
Safety and Tolerability as Defined as Number of Patients With Adverse Events
Safety and tolerability of the calorie-restricted, ketogenic diet and the transient fasting as defined as number of patients with adverse events
Time frame: day 1-12