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Trial registered on ANZCTR


Registration number
ACTRN12614001056684
Ethics application status
Approved
Date submitted
19/09/2014
Date registered
3/10/2014
Date last updated
24/04/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Pilot study of a ketogenic (low-carbohydrate) diet in patients receiving chemotherapy and radiation for glioblastoma multiforme (aggressive brain tumour)
Scientific title
Pilot study evaluating progression-free survival in patients using a ketogenic diet while receiving chemoradiation for glioblastoma multiforme
Secondary ID [1] 285368 0
None
Universal Trial Number (UTN)
U1111-1161-9611
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma multiforme 293100 0
Condition category
Condition code
Cancer 293374 293374 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Ketogenic diet (<30g carbohydrate per day) starting one week prior to standard treatment and continuing until all planned treatment has been completed. Patients will attend a 1 hour session with a dietitian at baseline to go through the dietary guidelines.

Standard treatment consists of 60 Gy radiation in 30 fractions over 6 weeks with concurrent daily oral temozolomide 75 mg/m2 (for no longer than 49 days); four weeks after completion of radiation patients will start six cycles of adjuvant temozolomide, taken orally daily days 1-5 of the 28-day cycle; the daily dose is 150 mg/m2 in the first adjuvant cycle then, if well-tolerated haematologically, 200 mg/m2 for remaining cycles, as tolerated.
Intervention code [1] 290283 0
Lifestyle
Intervention code [2] 290343 0
Treatment: Drugs
Intervention code [3] 290344 0
Treatment: Other
Comparator / control treatment
Standard treatment: 60 Gy radiation in 30 fractions over 6 weeks with concurrent daily oral temozolomide 75 mg/m2 (for no longer than 49 days); four weeks after completion of radiation patients will start six cycles of adjuvant temozolomide, taken orally daily days 1-5 of the 28-day cycle; the daily dose is 150 mg/m2 in the first adjuvant cycle then, if well-tolerated haematologically, 200 mg/m2 for remaining cycles, as tolerated. Patients received no dietary instructions during treatment. Historical patient data was collected from Waikato Hospital records for patients diagnosed with glioblastoma multiforme between 2007 and 2013 inclusive.
Control group
Historical

Outcomes
Primary outcome [1] 293202 0
Progression-free survival
Timepoint [1] 293202 0
Eight months after starting chemoradiation
Secondary outcome [1] 310570 0
Compliance with the ketogenic diet, assessed by the dietitian from 3-day food diaries and 24-hour food intake recalls.
Timepoint [1] 310570 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [2] 310571 0
Achievement of ketosis on urinary dipstick testing
Timepoint [2] 310571 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [3] 310572 0
Proportion of patients with adverse events considered possibly, probably or definitely related to the ketogenic diet (assessed by enquiry about adverse events at weekly review). Such adverse events may include fatigue, constipation, stomach cramps, halitosis and cravings.
Timepoint [3] 310572 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [4] 310574 0
Compliance with CRT and adjuvant chemotherapy, assessed from treatment charts.
Timepoint [4] 310574 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [5] 310575 0
patient-generated subjective global assessment (of malnutrition, nutritional intake and appetite)
Timepoint [5] 310575 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [6] 310576 0
Food satisfaction (assessed by a visual analogue scale)
Timepoint [6] 310576 0
1, 2, 4, 7, 11, 15, 19, 23, 27, 31 and 35 weeks from starting chemoradiation
Secondary outcome [7] 310577 0
Progression-free survival
Timepoint [7] 310577 0
Three months after commencing chemoradiation

Eligibility
Key inclusion criteria
* Patients with biopsy-proven glioblastoma multiforme who are considered suitable for standard chemoradiation (including adequate performance status and bone marrow, hepatic and liver function).
* Patients must be mentally competent to understand the requirements of the diet and believe that they, with the support of their carers, are capable of achieving them.
* Patients have given written informed consent
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Diabetic patients who are at risk of hypoglycaemic events (such as those on insulin or sulphonylureas)
* Current pregnancy or breast-feeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All consenting patients will receive the ketogenic diet and standard treatment
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Nil
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The primary objective of the study is to determine progression-free survival at 8 months from comencement of chemoradiation. Intention-to-treat analyses will be conducted.
If the true progression-free survival rate at 8 months is 75% then a sample size of 20 will give a 95% confidence interval of 53.6–89.8%, which does not overlap the observed progression-free survival of 45% at 8 months in a previous randomised trial. A result falling within this 95% CI would be of sufficient interest to warrant a larger randomised trial.
The remaining analyses will primarily use descriptive statistics as they are non-comparative. For repeated assessments over time (such as patient-reported outcomes) repeated measures ANOVA will be employed. A p value < 0.05 (two-sided) is considered statistically significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 6369 0
New Zealand
State/province [1] 6369 0
Waikato

Funding & Sponsors
Funding source category [1] 289981 0
Charities/Societies/Foundations
Name [1] 289981 0
Waikato Medical Research Foundation
Address [1] 289981 0
Peter Rothwell Academic Centre
Private Bag 3200
Hamilton 3240
Country [1] 289981 0
New Zealand
Primary sponsor type
Hospital
Name
Waikato District Health Board
Address
Pembroke Street
Private Bag 3200
Hamilton 3240
Country
New Zealand
Secondary sponsor category [1] 288666 0
None
Name [1] 288666 0
Address [1] 288666 0
Country [1] 288666 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291690 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 291690 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 291690 0
New Zealand
Date submitted for ethics approval [1] 291690 0
09/10/2014
Approval date [1] 291690 0
03/11/2014
Ethics approval number [1] 291690 0

Summary
Brief summary
Chemotherapy and radiotherapy for the most aggressive form of primary brain tumour, glioblastoma multiforme (GBM), offers only modest disease control, with half of all patients having disease progression before finishing their 8 month treatment programme, and about 3/4 dying within 2 years. Strategies to improve survival have largely been ineffective.
These tumours are almost completely reliant on glucose for fuel, and laboratory studies have reported that radiation treatment for GBM is much more effective when mice are fed a diet extremely low in carbohydrates. Such a diet is called “Ketogenic”, because the body generates ketones (the smell is like green apples) as an alternative fuel source for the brain and other organs. Such diets have been used for decades to help control seizures in children with epilepsy. There are case reports in the literature of patients with GBM who use these diets while on chemotherapy and radiation without apparent ill effects, and their outcomes appear encouraging.
However a more careful analysis of patients trying these diets is important to know how well most patients tolerate such a diet, whether it is safe during treatment, whether they enjoy their food and maintain a good nutritional status and whether there appears to be an improved outcome compared to patients treated while having their usual diet. We plan to conduct a pilot study in 20 patients having chemotherapy and radiotherapy for GBM to answer these questions.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51538 0
Dr Michael Jameson
Address 51538 0
Oncology Dept
Waikato District Health Board
Private Bag 3200
Hamilton 3240
Country 51538 0
New Zealand
Phone 51538 0
+64 7 839 8899
Fax 51538 0
+64 7 839 8778
Email 51538 0
michael.jameson@waikatodhb.health.nz
Contact person for public queries
Name 51539 0
Dr Michael Jameson
Address 51539 0
Oncology Dept
Waikato District Health Board
Private Bag 3200
Hamilton 3240
Country 51539 0
New Zealand
Phone 51539 0
+64 7 839 8899
Fax 51539 0
+64 7 839 8778
Email 51539 0
michael.jameson@waikatodhb.health.nz
Contact person for scientific queries
Name 51540 0
Dr Michael Jameson
Address 51540 0
Oncology Dept
Waikato District Health Board
Private Bag 3200
Hamilton 3240
Country 51540 0
New Zealand
Phone 51540 0
+64 7 839 8899
Fax 51540 0
+64 7 839 8778
Email 51540 0
michael.jameson@waikatodhb.health.nz

No information has been provided regarding IPD availability
Summary results
No Results