Calorie-restricted, Ketogenic Diet and Transient Fasting During Reirradiation for Patients With Recurrent Glioblastoma

Study Overview
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Brief Summary
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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.

Official Title
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Calorie-restricted, Ketogenic Diet and Transient Fasting vs. Standard Nutrition During Reirradiation for Patients With Recurrent Glioblastoma: the ERGO2 Study

Conditions
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Recurrent Glioblastoma

Intervention / Treatment
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* Dietary Supplement: calorie-restricted ketogenic diet and transient fasting
* Dietary Supplement: standard nutrition


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ketogenic diet and transient fasting<br>Calorie-restricted, ketogenic diet and transient fasting during reirradiation | Dietary Supplement: calorie-restricted ketogenic diet and transient fasting<br>* 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.<br>|
| Active Comparator: standard nutrition<br>nutrition according to recommendations of the German society for nutrition during reirradiation | Dietary Supplement: standard nutrition<br>* nutrition as recommended by the german society for nutrition, 30 kcal/kg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free-survival | Progression-free-survival rates 6 months after reirradiation based on response assessment in neuro-oncology criteria (RANO) | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | day 1-12 | 
| 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 | day 1-12 | 
| Progression-free-survival | progression-free-survival rates 1 month and 3 month after reirradiation | 1 month, 3 months | 
| Overall Survival | overall survival after the reirradiation | 12 months | 
| Frequency of Seizures | frequency of seizures at day 1-12 | day 1-12 | 
| Ketosis | urine and blood ketosis and metabolic parameters (glucose, insulin, IGF-1) during day 1-12 | day 1-12 | 
| 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 | day 1-12 | 
| Depression | depression as measured by SCL-90 at day 1-12 | day 1-12 | 
| Attention | attention as measured by d2-testing at day 1-12 | day 1-12 | 
| Response | response assessment 1 month after reirradiation | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ketogenic diet, glioma, fasting, reirradiation, nutrition