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

Primary Purpose

Glioblastoma Multiforme of Brain

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ketogenic Diet

Standardized Diet

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme of Brain focused on measuring Glioblastoma multigorme, Ketogenic Diet, radiotherapy, chemotherapy, safety, efficiency

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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)
Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment
Planned continued use of glucocorticoids
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)
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
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
History of uncontrolled hyperlipidemia
Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements
History of human immunodeficiency virus, or hepatitis C
Failure to recover from <CTCAE grade 2 toxicities related to prior therapy
Pregnancy or breastfeeding
Use of any investigational drug within 1 months of enrollment
Inability or unwillingness of subject to give written informed consent

Sites / Locations

MidAtlantic Epilepsy and Sleep Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Other

Arm Label

Ketogenic Diet

Standardized diet

Arm Description

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.

The subjects will be taken standard diet in a 1:1 ratio.

Outcomes

Primary Outcome Measures

survival time

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.

time to radiological (MRI) tumor progression

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.

The incidence of treatment-emergent adverse events during treatment

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

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

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

Full Information

NCT ID

NCT02302235

First Posted

November 24, 2014

Last Updated

August 10, 2022

Sponsor

Mid-Atlantic Epilepsy and Sleep Center, LLC

Collaborators

Neuroscience Research Foundation, Sewickley,PA

1. Study Identification

Unique Protocol Identification Number

NCT02302235

Brief Title

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

Acronym

GBMXRT

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

February 2014 (undefined)

Primary Completion Date

December 2021 (Actual)

Study Completion Date

May 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mid-Atlantic Epilepsy and Sleep Center, LLC

Collaborators

Neuroscience Research Foundation, Sewickley,PA

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma Multiforme of Brain

Keywords

Glioblastoma multigorme, Ketogenic Diet, radiotherapy, chemotherapy, safety, efficiency

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Ketogenic Diet

Arm Type

Active Comparator

Arm Description

Arm Title

Standardized diet

Arm Type

Other

Arm Description

The subjects will be taken standard diet in a 1:1 ratio.

Intervention Type

Other

Intervention Name(s)

Ketogenic Diet

Other Intervention Name(s)

KGD

Intervention Description

Treatment will consist of ketogenic diet. KD will consist of 4:1 [fat] : [protein+carbohydrate] weight ratio with 1600 kcal restriction.

Intervention Type

Other

Intervention Name(s)

Standardized Diet

Intervention Description

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.

Primary Outcome Measure Information:

Title

survival time

Description

Time Frame

6 months

Title

time to radiological (MRI) tumor progression

Description

Time Frame

6 months

Title

The incidence of treatment-emergent adverse events during treatment

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age 18-65 Ability and willingness to signed informed consent form Astrocytoma grade 4 (glioblastoma multiforme, GBM, histologically confirmed, WHO criteria) Documented surgical resection/debulking Measurable contrast-enhancing GBM by MRI imaging ≤ two weeks before screening or prior to surgery if done ≤ 2 months before Karnovsky Performance Score of 70 or more Exclusion Criteria: 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) Prior treatment with any of the following: (a) small-molecule kinase inhibitor; (b) non-cytotoxic hormonal agent; (c) KD ≤6 months of enrollment Planned continued use of glucocorticoids 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) 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 History of non-glioma malignancy other than: Surgically excised non-melanoma skin cancer or in situ carcinoma of the cervix A malignancy diagnosed ≥2 years ago if the subject has had no evidence of disease for 2 years prior to screening History of uncontrolled hyperlipidemia Active drug or alcohol dependence or any other factors that, in the opinion of the site investigators would interfere with adherence to study requirements History of human immunodeficiency virus, or hepatitis C Failure to recover from <CTCAE grade 2 toxicities related to prior therapy Pregnancy or breastfeeding Use of any investigational drug within 1 months of enrollment Inability or unwillingness of subject to give written informed consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pavel Klein, M.D.

Organizational Affiliation

Mid-Atlantic Epilepsy and Sleep Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

MidAtlantic Epilepsy and Sleep Center

City

Bethesda

State/Province

Maryland

ZIP/Postal Code

20817

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33292598

Citation

Klein P, Tyrlikova I, Zuccoli G, Tyrlik A, Maroon JC. Treatment of glioblastoma multiforme with "classic" 4:1 ketogenic diet total meal replacement. Cancer Metab. 2020 Nov 9;8(1):24. doi: 10.1186/s40170-020-00230-9.

Results Reference

derived

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

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