GlioblastomaNCT04730869
Metabolic Therapy Program In Conjunction With Standard Treatment For Glioblastoma
A study testing Standard Treatment Plus Metabolic Therapy Program in people with Glioblastoma, run by Waikato Hospital at 1 site in New Zealand.
Trial summary
Glioblastoma (GBM), a very aggressive brain tumour, is one of the most malignant of all cancers and is associated with a poor prognosis. The majority of GBM cells display damaged mitochondria (the "batteries" of cells), so they rely on an alternate method for producing energy called the Warburg Effect, which relies… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Standard Treatment Plus Metabolic Therapy Program
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteNew Zealand
- Study dates
- 26 May 2021to 1 Apr 2026
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years or greater.
- Newly-diagnosed histologically-confirmed GBM.
- ECOG Performance Status 0-2.
- Planned for 6 weeks of standard chemoradiation for GBM.
- If receiving dexamethasone, the dose must be ≤ 4 mg daily (and not increasing) upon commencement of the MTP.
Who cannot join
- Ineligible for standard treatment for GBM due to poor performance status, co-morbidities, or inability to give informed consent.
- Type 1 diabetes.
- A medical or psychiatric disorder that, in the opinion of the investigators, would make it unlikely that the patient could adhere to the MTP.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Feasibility, Safety, and Efficacy of a Metabolic Therapy Program in Conjunction With Standard Treatment for Glioblastoma
Glioblastoma (GBM), a very aggressive brain tumour, is one of the most malignant of all cancers and is associated with a poor prognosis. The majority of GBM cells display damaged mitochondria (the "batteries" of cells), so they rely on an alternate method for producing energy called the Warburg Effect, which relies nearly exclusively on glucose (in contrast, normal cells can use other molecules, such as fatty acids and fat-derived ketones, for energy). Metabolic interventions, such as fasting and ketogenic diets, target cancer cell metabolism by enhancing mitochondria function, decreasing blood glucose levels, and increasing blood ketone levels, creating an advantage for normal cells but a disadvantage for cancer cells. Preliminary experience at Waikato Hospital has shown that a metabolic therapy program (MTP) utilizing fasting and ketogenic diets is feasible and safe in people with advanced cancer, and may provide a therapeutic benefit. We aim to determine whether using an MTP concurrently with standard oncological treatment (chemoradiation followed by adjuvant chemotherapy) is feasible and safe in patients with GBM, and has treatment outcomes consistent with greater overall treatment efficacy than in published trials.
Read the detailed description
Gliomas are tumours that originate from glial cells in the central nervous system. The most common histological subtype is GBM, which accounts for nearly 50% of all malignant brain tumours. Despite aggressive multimodal treatment, the median survival for GBM is poor (8-15 months).
Although cancer is regarded as a genetic disease, it may be perceived as a metabolic disorder. The majority of human cancers, including GBM, display low numbers of mitochondria, most of which are structurally damaged, resulting in defective cell respiration. To compensate, cancer cells greatly increase their uptake of glucose, which is fermented (regardless of oxygen concentration, a process known as the Warburg Effect) to generate energy. Cancer cells also rely on increased growth signaling pathways involving insulin, insulin-like growth factor-1, and mammalian target of rapamycin to support their unbridled growth and proliferation. Cancer cells may therefore be vulnerable to interventions that selectively target their abnormal metabolism.
Metabolic interventions, such as fasting and ketogenic diets, target cancer cell metabolism and may be effective alongside standard treatments in advanced cancers. Fasting is a voluntary abstinence from food and drink for a controlled period of time (typically, 12 hours to 3 weeks in humans), whereas ketogenic diets are high-fat, adequate-protein, low-carbohydrate diets that stimulate the body to create a fasting-like metabolic state. Fasting and ketogenic diets stimulate mitochondria biogenesis, decrease blood glucose, increase liver production of fat-derived ketones (which serve as a major alternative energy source for most normal cells within the body, but cannot be utilized by cancer cells), and decrease growth factor availability. Thus, fasting and ketogenic diets provide an advantage for normal cells but a disadvantage to cancer cells by enhancing mitochondria biogenesis and function, depriving cancer cells of their major fuel, and creating a cell environment unfavourable for unbridled growth and proliferation.
Preliminary experience at Waikato Hospital has shown that a metabolic therapy program (MTP) consisting of fasting and/or a ketogenic diet is feasible, safe, and may be effective in patients with advanced cancer, including GBM. In a recent case report, a metabolic strategy (7-day fast every 1-2 months, with a ketogenic diet between fasts) resulted in the near-complete regression of a stage IVA metastatic thymoma after 2 years. Moreover, we are currently observing 8 glioblastoma patients who voluntarily consented to undergo fasting and ketogenic diet therapy in a manner similar to what we propose to use in this study; at an average of 4-5 months, all patients have completed the fasts and adhered to their ketogenic diet, experiencing only mild adverse effects.
On this background, we aim to determine whether using an MTP concurrently with standard oncological treatment (chemoradiation followed by adjuvant chemotherapy) is feasible and safe, and has treatment outcomes consistent with greater overall treatment efficacy than in published trials, in patients with GBM.
- Conditions
- Glioblastoma
- Being tested
- Standard Treatment Plus Metabolic Therapy Program
- Keywords
- cancer, glioblastoma, metabolic therapy, fasting, ketogenic diet
- Medical subject headings
- Glioblastoma, Neoplasms, Fasting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standard Treatment Plus Metabolic Therapy ProgramOther
See description under "Arms."
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment in conjunction with MTP | Experimental | Standard:
* Concurrent chemoradiation - Radiation (60-Gy in 30 fractions over 6 weeks) with daily oral temozolomide.
* Adjuvant chemotherapy - Daily oral temozolomide (5 days per 4-week cycle, starting 4 weeks after completion of chemoradiation, with at least 6 cycles intended).
MTP:
- Two 5-day fasts (allowing water, salt, tea, coffee, and a magnesium supplement) during chemoradiation followed by a 5-day fast during each adjuvant chemotherapy cycle, with a time-restricted modified ketogenic diet (one or two 1-hour eating windows per day, allowing oils, meats, vegetables, nuts, seeds, limited berries, and a multivitamin) between fasts. Receives: Other: Standard Treatment Plus Metabolic Therapy Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean daily blood glucose-to-ketone ratio during chemoradiation
Proportion of patients able to sustain functional ketosis (defined as a mean daily blood glucose-to-ketone ratio of ≤6) during chemoradiation (defined as the beginning of the first fast through to 3 weeks following completion of chemoradiation)
Measured: 9 weeks
Secondary outcomes (9)
Mean daily blood glucose-to-ketone ratio during adjuvant chemotherapy
Proportion of patients able to sustain functional ketosis during adjuvant chemotherapy (defined as the beginning of the first adjuvant chemotherapy fast through to completion of adjuvant chemotherapy)
Measured: 24 weeks
Mean daily blood glucose-to-ketone ratio during the MTP, calculated separately on fasting and ketogenic diet days
Proportion of patients able to sustain functional ketosis during the MTP (defined as the beginning of chemoradiation through to the end of adjuvant chemotherapy), calculated separately each fasting and ketogenic diet phase
Measured: 33 weeks
Change in weight
Weight (kg)
Measured: 33 weeks
Safety as measured by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4)
Number of adverse events (of any grade)
Measured: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in performance status as measured by Eastern Cooperative Oncology Group Performance Status scale
Eastern Cooperative Oncology Group Performance Status scale (scores range from 0 to 5, with higher scores indicating lower performance status)
Measured: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in leisure/exercise activity as measured by Godin Leisure-Time Exercise questionnaire
Godin Leisure-Time Exercise questionnaire (scores range from 0 to no maximum, with higher scores indicating higher leisure/exercise activity)
Measured: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in quality of life as measured by Functional Assessment of Cancer Therapy - Brain questionnaire
Functional Assessment of Cancer Therapy - Brain questionnaire (scores range from 0 to 200, with higher scores indicating higher quality of life)
Measured: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Progression-free survival
Progression-free survival
Measured: From date of biopsy-confirmed diagnosis to date of first documented progression, whichever came first, up to 33 weeks
Overall survival
Overall survival
Measured: From date of biopsy-confirmed diagnosis to date of death from any cause, whichever came first, up to 33 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2021
- Study start26 May 2021
- Primary completion18 Feb 2025
- Study completion1 Apr 2026
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 GlioblastomaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Waikato Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Wellington Hospital
- Responsible party
- Sponsor
- Investigators
- Matthew CL Phillips, FRACP, Principal investigator, Waikato Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04730869
- Sponsor's protocol ID
- RD020132
- Other IDs
- U1111-1262-0203, Grant #321
- Status last verified
- Aug 2026
- First submitted
- 22 Dec 2020
- Last updated
- 6 Aug 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon reasonable request for research purposes only, de-identified patient data may be shared with other investigators.
Publications
Phillips MCL, Thotathil Z, Haji Mohd Yasin NAB, de Groot C, Tan A, Kuper-Hommel M, Creagh LA, Ji E, Naidoo N, van Essen M, Ziad F, Moon BG, Frampton C, Jameson MB. Intensive multimodal ketogenic metabolic therapy in glioblastoma: A clinical trial. Neurooncol Adv. 2026 Jun 29;8(1):vdag165. doi: 10.1093/noajnl/vdag165. eCollection 2026 Jan-Dec.
PubMed 42542667
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility, Safety, and Efficacy of a Metabolic Therapy Program in Conjunction With Standard Treatment for Glioblastoma
- ClinicalTrials.gov ID
- NCT04730869
- Acronym / sponsor ID
- RD020132
- Conditions
- Glioblastoma
- Keywords
- cancer, glioblastoma, metabolic therapy, fasting, ketogenic diet
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Waikato HospitalUniversity, hospital or other
- Collaborators
- Wellington Hospital
- Study start
- 26 May 2021 (actual)
- Primary completion
- 18 Feb 2025 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 29 Jan 2021 (actual)
- 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.
Glioblastoma (GBM), a very aggressive brain tumour, is one of the most malignant of all cancers and is associated with a poor prognosis. The majority of GBM cells display damaged mitochondria (the "batteries" of cells), so they rely on an alternate method for producing energy called the Warburg Effect, which relies nearly exclusively on glucose (in contrast, normal cells can use other molecules, such as fatty acids and fat-derived ketones, for energy). Metabolic interventions, such as fasting and ketogenic diets, target cancer cell metabolism by enhancing mitochondria function, decreasing blood glucose levels, and increasing blood ketone levels, creating an advantage for normal cells but a disadvantage for cancer cells. Preliminary experience at Waikato Hospital has shown that a metabolic therapy program (MTP) utilizing fasting and ketogenic diets is feasible and safe in people with advanced cancer, and may provide a therapeutic benefit. We aim to determine whether using an MTP concurrently with standard oncological treatment (chemoradiation followed by adjuvant chemotherapy) is feasible and safe in patients with GBM, and has treatment outcomes consistent with greater overall treatment efficacy than in published trials.
Detailed description
Gliomas are tumours that originate from glial cells in the central nervous system. The most common histological subtype is GBM, which accounts for nearly 50% of all malignant brain tumours. Despite aggressive multimodal treatment, the median survival for GBM is poor (8-15 months).
Although cancer is regarded as a genetic disease, it may be perceived as a metabolic disorder. The majority of human cancers, including GBM, display low numbers of mitochondria, most of which are structurally damaged, resulting in defective cell respiration. To compensate, cancer cells greatly increase their uptake of glucose, which is fermented (regardless of oxygen concentration, a process known as the Warburg Effect) to generate energy. Cancer cells also rely on increased growth signaling pathways involving insulin, insulin-like growth factor-1, and mammalian target of rapamycin to support their unbridled growth and proliferation. Cancer cells may therefore be vulnerable to interventions that selectively target their abnormal metabolism.
Metabolic interventions, such as fasting and ketogenic diets, target cancer cell metabolism and may be effective alongside standard treatments in advanced cancers. Fasting is a voluntary abstinence from food and drink for a controlled period of time (typically, 12 hours to 3 weeks in humans), whereas ketogenic diets are high-fat, adequate-protein, low-carbohydrate diets that stimulate the body to create a fasting-like metabolic state. Fasting and ketogenic diets stimulate mitochondria biogenesis, decrease blood glucose, increase liver production of fat-derived ketones (which serve as a major alternative energy source for most normal cells within the body, but cannot be utilized by cancer cells), and decrease growth factor availability. Thus, fasting and ketogenic diets provide an advantage for normal cells but a disadvantage to cancer cells by enhancing mitochondria biogenesis and function, depriving cancer cells of their major fuel, and creating a cell environment unfavourable for unbridled growth and proliferation.
Preliminary experience at Waikato Hospital has shown that a metabolic therapy program (MTP) consisting of fasting and/or a ketogenic diet is feasible, safe, and may be effective in patients with advanced cancer, including GBM. In a recent case report, a metabolic strategy (7-day fast every 1-2 months, with a ketogenic diet between fasts) resulted in the near-complete regression of a stage IVA metastatic thymoma after 2 years. Moreover, we are currently observing 8 glioblastoma patients who voluntarily consented to undergo fasting and ketogenic diet therapy in a manner similar to what we propose to use in this study; at an average of 4-5 months, all patients have completed the fasts and adhered to their ketogenic diet, experiencing only mild adverse effects.
On this background, we aim to determine whether using an MTP concurrently with standard oncological treatment (chemoradiation followed by adjuvant chemotherapy) is feasible and safe, and has treatment outcomes consistent with greater overall treatment efficacy than in published trials, in patients with GBM.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Standard treatment in conjunction with MTP | Experimental | Other: Standard Treatment Plus Metabolic Therapy ProgramStandard: * Concurrent chemoradiation - Radiation (60-Gy in 30 fractions over 6 weeks) with daily oral temozolomide. * Adjuvant chemotherapy - Daily oral temozolomide (5 days per 4-week cycle, starting 4 weeks after completion of chemoradiation, with at least 6 cycles intended). MTP: - Two 5-day fasts (allowing water, salt, tea, coffee, and a magnesium supplement) during chemoradiation followed by a 5-day fast during each adjuvant chemotherapy cycle, with a time-restricted modified ketogenic diet (one or two 1-hour eating windows per day, allowing oils, meats, vegetables, nuts, seeds, limited berries, and a multivitamin) between fasts. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age 18 years or greater.
- Newly-diagnosed histologically-confirmed GBM.
- ECOG Performance Status 0-2.
- Planned for 6 weeks of standard chemoradiation for GBM.
- If receiving dexamethasone, the dose must be ≤ 4 mg daily (and not increasing) upon commencement of the MTP.
Key exclusion criteria (3 listed)
- Ineligible for standard treatment for GBM due to poor performance status, co-morbidities, or inability to give informed consent.
- Type 1 diabetes.
- A medical or psychiatric disorder that, in the opinion of the investigators, would make it unlikely that the patient could adhere to the MTP.
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 |
|---|---|---|
| Standard Treatment Plus Metabolic Therapy ProgramSee description under "Arms." | Other | Standard treatment in conjunction with MTP |
Primary outcome
Mean daily blood glucose-to-ketone ratio during chemoradiation
Time frame: 9 weeks
Proportion of patients able to sustain functional ketosis (defined as a mean daily blood glucose-to-ketone ratio of ≤6) during chemoradiation (defined as the beginning of the first fast through to 3 weeks following completion of chemoradiation)
9 secondary outcomes
Mean daily blood glucose-to-ketone ratio during adjuvant chemotherapy
Time frame: 24 weeks
Mean daily blood glucose-to-ketone ratio during the MTP, calculated separately on fasting and ketogenic diet days
Time frame: 33 weeks
Change in weight
Time frame: 33 weeks
Safety as measured by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4)
Time frame: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in performance status as measured by Eastern Cooperative Oncology Group Performance Status scale
Time frame: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in leisure/exercise activity as measured by Godin Leisure-Time Exercise questionnaire
Time frame: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Change in quality of life as measured by Functional Assessment of Cancer Therapy - Brain questionnaire
Time frame: After each week (7 days) during chemoradiation, then after cycle 1 (28 days) of adjuvant chemotherapy, then after every 2 cycles (56 days) of adjuvant chemotherapy
Progression-free survival
Time frame: From date of biopsy-confirmed diagnosis to date of first documented progression, whichever came first, up to 33 weeks
Overall survival
Time frame: From date of biopsy-confirmed diagnosis to date of death from any cause, whichever came first, up to 33 weeks
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 6 Aug 2026.
- Background: PubMed 42542667Phillips MCL, Thotathil Z, Haji Mohd Yasin NAB, de Groot C, Tan A, Kuper-Hommel M, Creagh LA, Ji E, Naidoo N, van Essen M, Ziad F, Moon BG, Frampton C, Jameson MB. Intensive multimodal ketogenic metabolic therapy in glioblastoma: A clinical trial. Neurooncol Adv. 2026 Jun 29;8(1):vdag165. doi: 10.1093/noajnl/vdag165. eCollection 2026 Jan-Dec.
- Individual participant dataSharing planned: Yes. Upon reasonable request for research purposes only, de-identified patient data may be shared with other investigators.
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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.
Matthew CL Phillips, FRACP principal investigator
Waikato Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Standard Treatment Plus Metabolic Therapy Program in people with Glioblastoma, run by Waikato Hospital at 1 site in New Zealand.
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 5 inclusion and 3 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 6 Aug 2026. 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 New Zealand. 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.
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?
Mean daily blood glucose-to-ketone ratio during chemoradiation (time frame: 9 weeks). 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 NCT04730869, 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 6 Aug 2026.