Ketogenic Diet Treatment Adjunctive to Radiation and Chemotherapy in Glioblastoma Multiforme: a Pilot Study

Phase 2

Completed

• Conditions: Glioblastoma Multiforme of Brain
• Interventions: Other: Standardized Diet; Other: Ketogenic Diet

• Registration Number: NCT02302235
• Lead Sponsor: Mid-Atlantic Epilepsy and Sleep Center, LLC

Brief Summary

The goal of the present study is to evaluate efficacy, safety and tolerability of 4:1 ketogenic diet administered adjunctively to standard radiation and temozolomide chemotherapy in patients with GBM in a prospective, randomized open label study.

Detailed Description

Primary aims of the study will be to 1) To evaluate efficacy of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme. 2) To evaluate the safety of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme. Secondary aim will be to evaluate tolerability of ketogenic diet as adjunctive treatment of radiation treatment in glioblastoma multiforme.

Participants will be seen at one, 2 weeks, and 4 weeks after KG diet initiation, and then monthly until month 6 after diet initiation, then every 2 months until 2 years after treatment initiation or death, then every 3 months until 3 years after treatment initiation or death. KD treatment will last for 6 months or until exit criteria are met, whichever comes first. Exit criteria are the primary outcome measures, the first of either (a) MRI tumor progression or (b) death. Secondary outcome measures will include treatment compliance, hunger scale scores, fasting serum glucose and BOH levels and occurrence of adverse events.

Patients with documented tumor progression will receive standard care for progressive GBM as directed by their treating oncologist, independent of the study.

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-11-24
• Study First Submitted QC: 2014-11-25
• Study First Posted: 2014-11-26
• Primary Completion: 2021-12
• Study Completion: 2022-05
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-10
• Last Update Posted: 2022-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

1. Age 18-65
2. Ability and willingness to signed informed consent form
3. Astrocytoma grade 4 (glioblastoma multiforme, GBM, histologically confirmed, WHO criteria)
4. Documented surgical resection/debulking
5. Measurable contrast-enhancing GBM by MRI imaging ≤ two weeks before screening or prior to surgery if done ≤ 2 months before
6. Karnovsky Performance Score of 70 or more

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Exclusion Criteria

1. Acute intracranial or intratumoral hemorrhage > Grade 1 either by MRI or CT scan ≤2 weeks of screening. (Subjects with resolving hemorrhage changes, punctate hemorrhage, or hemosiderin may enter the study)

2. Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment

3. Planned continued use of glucocorticoids

4. Anticoagulation treatment with ≥ 1 mg/day coumadin ≤ 7 days prior to screening (low-dose [≤ 1 mg/day] coumadin, heparin, and low-molecular-weight heparin are permitted)

5. Any systemic illness or unstable medical condition that might pose additional risk, including: cardiac, unstable metabolic or endocrine disturbances, renal or liver disease, past history of renal calculi, hyperuricemia, hypercalcemia, mitochondrial disease, known disorder of fatty acid metabolism, porphyria, carnitine deficiency and pancreatitis

6. History of non-glioma malignancy other than:

   1. Surgically excised non-melanoma skin cancer or in situ carcinoma of the cervix
   2. A malignancy diagnosed ≥2 years ago if the subject has had no evidence of disease for 2 years prior to screening

7. History of uncontrolled hyperlipidemia

8. Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements

9. History of human immunodeficiency virus, or hepatitis C

10. Failure to recover from <CTCAE grade 2 toxicities related to prior therapy

11. Pregnancy or breastfeeding

12. Use of any investigational drug within 1 months of enrollment

13. Inability or unwillingness of subject to give written informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Ketogenic Diet	Standardized Diet	Treatment will consist of ketogenic diet. KGD will consist of 4:1 \[fat\] : \[protein+carbohydrate\] weight ratio with 1600 kcal restriction. Diet will be started at the time of initiation of radiation treatment.
Standardized diet	Ketogenic Diet	The subjects will be taken standard diet in a 1:1 ratio.

Primary Outcome Measures

Name	Time	Method
time to radiological (MRI) tumor progression	6 months	MRI outcome will be assessed by the radiographic assessment in neuro-oncology criteria based on contrast-enhanced cranial MRI scans evaluating measureable disease, measured as the sum of products of perpendicular diameters (bi-dimensional measurements) of all measurable enhancing lesions and non-measurable disease.
survival time	6 months	We hope to achieve a substantial difference in both survival time and time to recurrence between the KD and non-KD treatment groups. Survival time of 3 years from treatment initiation and tumor progression-free time of 2.5 years from treatment initiation would be extraordinary compared to historical data.
The incidence of treatment-emergent adverse events during treatment	6 months	Incidence of treatment-emergent adverse events changes in laboratory evaluations, changes in physical examination findings will be compared between the KD and control treatment groups

Secondary Outcome Measures

Name	Time	Method
Tolerability of ketogenic diet: Rate of early discontinuation of subjects from the diet because of intolerability, defined as unwillingness by the subject to continue with the diet because of possible diet related side effects	6 months	Rate of early discontinuation of subjects from the diet because of intolerability, defined as unwillingness by the subject to continue with the diet because of possible diet related side effects will be evaluated using descriptive statistics

Trial Locations

Locations (1)

MidAtlantic Epilepsy and Sleep Center; 🇺🇸 Bethesda, Maryland, United States