Glioblastoma Multiforme of BrainPhase 2GBMXRTNCT02302235
Ketogenic Diet Treatment Adjunctive to Radiation and Chemotherapy in Glioblastoma Multiforme: a Pilot Study
A Phase 2 study testing Ketogenic Diet and Standardized Diet in people with Glioblastoma Multiforme of Brain, run by Mid-Atlantic Epilepsy and Sleep Center, LLC at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Glioblastoma Multiforme of Brain
- What is being tested?
- Ketogenic Diet and Standardized Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2014to May 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
MidAtlantic Epilepsy and Sleep Center
Bethesda, Maryland, 20817
About this study
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.
Read the 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.
- Conditions
- Glioblastoma Multiforme of Brain
- Being tested
- Ketogenic Diet, Standardized Diet
- Keywords
- Glioblastoma multigorme, Ketogenic Diet, radiotherapy, chemotherapy, safety, efficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic DietOther
Also called KGD
Treatment will consist of ketogenic diet. KD will consist of 4:1 [fat] : [protein+carbohydrate] weight ratio with 1600 kcal restriction.
Standardized DietOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic Diet | Active comparator | 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. Receives: Other: Standardized Diet |
| Standardized diet | Other | The subjects will be taken standard diet in a 1:1 ratio. Receives: Other: Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
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.
Measured: 6 months
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
Measured: 6 months
Secondary outcomes (1)
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2014 (estimated)
- Study startFeb 2014
- Primary completionDec 2021
- Study completionMay 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Glioblastoma Multiforme of BrainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mid-Atlantic Epilepsy and Sleep Center, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Neuroscience Research Foundation, Sewickley,PA
- Responsible party
- Sponsor
- Investigators
- Pavel Klein, M.D., Principal investigator, Mid-Atlantic Epilepsy and Sleep Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02302235
- Sponsor's protocol ID
- maesc 006
- Acronym
- GBMXRT
- Status last verified
- Aug 2022
- First submitted
- 24 Nov 2014
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 33292598
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketogenic Diet Treatment Adjunctive to Radiation and Chemotherapy in Glioblastoma Multiforme: a Pilot Study
- ClinicalTrials.gov ID
- NCT02302235
- Acronym / sponsor ID
- GBMXRT / maesc 006
- Conditions
- Glioblastoma Multiforme of Brain
- Keywords
- Glioblastoma multigorme, Ketogenic Diet, radiotherapy, chemotherapy, safety, efficiency
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Mid-Atlantic Epilepsy and Sleep Center, LLCUniversity, hospital or other
- Collaborators
- Neuroscience Research Foundation, Sewickley,PA
- Study start
- Feb 2014
- Primary completion
- Dec 2021 (actual)
- Study completion
- May 2022 (actual)
- First posted
- 26 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketogenic Diet | Active comparator | Other: Standardized DietTreatment 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 | Other | Other: Ketogenic DietThe subjects will be taken standard diet in a 1:1 ratio. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic DietAlso: KGDTreatment will consist of ketogenic diet. KD will consist of 4:1 [fat] : [protein+carbohydrate] weight ratio with 1600 kcal restriction. | Other | Standardized diet |
| Standardized DietParticipants 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 | Ketogenic Diet |
Primary outcome
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.
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.
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- Derived from this study: PubMed 33292598Klein 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pavel Klein, M.D. principal investigator
Mid-Atlantic Epilepsy and Sleep Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketogenic Diet and Standardized Diet in people with Glioblastoma Multiforme of Brain, run by Mid-Atlantic Epilepsy and Sleep Center, LLC at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
survival time (time frame: 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02302235, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2022.