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

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.

Study Overview

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 Type

Interventional

Enrollment (Anticipated)

42

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Midatlantic Epilepsy and Sleep Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ketogenic 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.
Participants with GBM treated with radiation and temozolomide after surgical debulking treatment. The subjects will be taken standard diet in a 1:1 ratio. Diet will be started at the time of initiation of radiation treatment.
Other: Standardized diet
The subjects will be taken standard diet in a 1:1 ratio.
Treatment will consist of ketogenic diet. KD will consist of 4:1 [fat] : [protein+carbohydrate] weight ratio with 1600 kcal restriction.
Other Names:
  • KGD

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
survival time
Time Frame: 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.
6 months
time to radiological (MRI) tumor progression
Time Frame: 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.
6 months
The incidence of treatment-emergent adverse events during treatment
Time Frame: 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
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Pavel Klein, M.D., Mid-Atlantic Epilepsy and Sleep Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

December 1, 2021

Study Completion (Actual)

May 1, 2022

Study Registration Dates

First Submitted

November 24, 2014

First Submitted That Met QC Criteria

November 25, 2014

First Posted (Estimate)

November 26, 2014

Study Record Updates

Last Update Posted (Actual)

August 11, 2022

Last Update Submitted That Met QC Criteria

August 10, 2022

Last Verified

August 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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