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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04730869




Registration number
NCT04730869
Ethics application status
Date submitted
22/12/2020
Date registered
29/01/2021
Date last updated
3/08/2023

Titles & IDs
Public title
Metabolic Therapy Program In Conjunction With Standard Treatment For Glioblastoma
Scientific title
Feasibility, Safety, and Efficacy of a Metabolic Therapy Program in Conjunction With Standard Treatment for Glioblastoma
Secondary ID [1] 0 0
U1111-1262-0203
Secondary ID [2] 0 0
RD020132
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Standard Treatment Plus Metabolic Therapy Program

Experimental: Standard treatment in conjunction with MTP - 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.


Other interventions: Standard Treatment Plus Metabolic Therapy Program
See description under "Arms."
Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean daily blood glucose-to-ketone ratio during chemoradiation
Timepoint [1] 0 0
9 weeks
Secondary outcome [1] 0 0
Mean daily blood glucose-to-ketone ratio during adjuvant chemotherapy
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Mean daily blood glucose-to-ketone ratio during the MTP, calculated separately on fasting and ketogenic diet days
Timepoint [2] 0 0
33 weeks
Secondary outcome [3] 0 0
Change in weight
Timepoint [3] 0 0
33 weeks
Secondary outcome [4] 0 0
Safety as measured by National Cancer Institute Common Terminology Criteria for Adverse Events (version 4)
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
Change in performance status as measured by Eastern Cooperative Oncology Group Performance Status scale
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Change in leisure/exercise activity as measured by Godin Leisure-Time Exercise questionnaire
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Change in quality of life as measured by Functional Assessment of Cancer Therapy - Brain questionnaire
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
Progression-free survival
Timepoint [8] 0 0
From date of biopsy-confirmed diagnosis to date of first documented progression, whichever came first, up to 33 weeks
Secondary outcome [9] 0 0
Overall survival
Timepoint [9] 0 0
From date of biopsy-confirmed diagnosis to date of death from any cause, whichever came first, up to 33 weeks

Eligibility
Key inclusion criteria
1. Age 18 years or greater.

2. Newly-diagnosed histologically-confirmed GBM.

3. ECOG Performance Status 0-2.

4. Planned for 6 weeks of standard chemoradiation for GBM.

5. If receiving dexamethasone, the dose must be = 4 mg daily (and not increasing) upon
commencement of the MTP.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Ineligible for standard treatment for GBM due to poor performance status,
co-morbidities, or inability to give informed consent.

2. Type 1 diabetes.

3. A medical or psychiatric disorder that, in the opinion of the investigators, would
make it unlikely that the patient could adhere to the MTP.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2024
Actual
Sample size
Target
22
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
New Zealand
State/province [1] 0 0
Waikato

Funding & Sponsors
Primary sponsor type
Other
Name
Waikato Hospital
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Wellington Hospital
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04730869
Trial related presentations / publications
Rajaratnam V, Islam MM, Yang M, Slaby R, Ramirez HM, Mirza SP. Glioblastoma: Pathogenesis and Current Status of Chemotherapy and Other Novel Treatments. Cancers (Basel). 2020 Apr 10;12(4):937. doi: 10.3390/cancers12040937.
Anjum K, Shagufta BI, Abbas SQ, Patel S, Khan I, Shah SAA, Akhter N, Hassan SSU. Current status and future therapeutic perspectives of glioblastoma multiforme (GBM) therapy: A review. Biomed Pharmacother. 2017 Aug;92:681-689. doi: 10.1016/j.biopha.2017.05.125. Epub 2017 Jun 3. Erratum In: Biomed Pharmacother. 2018 Mar 8;101:820.
Seyfried BT, Kiebish M, Marsh J, Mukherjee P. Targeting energy metabolism in brain cancer through calorie restriction and the ketogenic diet. J Cancer Res Ther. 2009 Sep;5 Suppl 1:S7-15. doi: 10.4103/0973-1482.55134.
Seyfried TN. Cancer as a mitochondrial metabolic disease. Front Cell Dev Biol. 2015 Jul 7;3:43. doi: 10.3389/fcell.2015.00043. eCollection 2015.
Seyfried TN, Flores RE, Poff AM, D'Agostino DP. Cancer as a metabolic disease: implications for novel therapeutics. Carcinogenesis. 2014 Mar;35(3):515-27. doi: 10.1093/carcin/bgt480. Epub 2013 Dec 16.
Phillips MCL. Fasting as a Therapy in Neurological Disease. Nutrients. 2019 Oct 17;11(10):2501. doi: 10.3390/nu11102501.
Phillips MCL, Murtagh DKJ, Sinha SK, Moon BG. Managing Metastatic Thymoma With Metabolic and Medical Therapy: A Case Report. Front Oncol. 2020 May 5;10:578. doi: 10.3389/fonc.2020.00578. eCollection 2020.
Public notes

Contacts
Principal investigator
Name 0 0
Matthew CL Phillips, FRACP
Address 0 0
Waikato Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Matthew CL Phillips, FRACP
Address 0 0
Country 0 0
Phone 0 0
+64274057415
Fax 0 0
Email 0 0
Matthew.Phillips@waikatodhb.health.nz
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04730869