Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001201763
Ethics application status
Approved
Date submitted
30/06/2022
Date registered
7/09/2022
Date last updated
7/09/2022
Date data sharing statement initially provided
7/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Targeting the Renin-Angiotensin System in Glioblastoma (TRAS-GB) Trial
Scientific title
Efficacy of Treatment Targeting the Renin-Angiotensin System in Glioblastoma (TRAS-GB) Trial
Secondary ID [1] 307451 0
none
Universal Trial Number (UTN)
U1111-1268-0050
Trial acronym
TRAS-GB
Linked study record
ACTRN12619001078145; this is the previous Phase I trial.
TRAS-GB is the follow on Phase II trial.

Health condition
Health condition(s) or problem(s) studied:
Glioblastoma 326828 0
Condition category
Condition code
Cancer 324041 324041 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study medication is introduced in a step-wise manner, starting 4 weeks after completion of surgery and radiotherapy and the first cycle of chemotherapy (Temozolomide (TMZ)).

The study treatment consists of six oral medications. The dosage of the medications is increased over a 4 week period, and the treatment is maintained for the duration of the study. The total duration of the study is 4 years.

The dosing regime is as follows;
1) Propranolol; week 0 - 40mg twice daily, week 1 - 80mg morning, 40mg evening, continue at this dose for the remainder of the study
2) Aliskiren; week 0 - 150mg once daily, continue at this dose for the remainder of the study
3) Curcumin with piperine; week 0 - 1000mg twice daily, continue at this dose for the remainder of the study
4) Celecoxib; introduced at week 4 - 200mg once daily, continue at this dose for the remainder of the study
5) Metformin; week 0 - 250mg once daily, week 1 - 250mg twice daily, week 3 - 500mg morning, 250mg evening, week 4 - 500mg twice daily, continue at this dose for the remainder of the study
6) Quinapril; introduced at week 2 - 5mg once daily, week 3 - 10mg once daily, week 4 - 20mg once daily, continue at this dose for the remainder of the study

Renal function, platelet count, blood pressure and pulse rate are monitored.
Intervention code [1] 323903 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331832 0
Overall median survival from diagnosis
Timepoint [1] 331832 0
Assessed on an ongoing basis for study duration. The study is planned for a 4 year duration.
Secondary outcome [1] 411336 0
Survival after initiation of trial treatment regime
Timepoint [1] 411336 0
Assessed on an ongoing basis for study duration. The study is planned for a 4 year duration.
Secondary outcome [2] 411337 0
Rate of radiological tumour progression. This is assessed by serial FET PET scans.
Timepoint [2] 411337 0
5 weeks post-commencement of trial medications (baseline), and then 4, 9, 18 and 36 months after final TMZ dose
Secondary outcome [3] 411338 0
Change in quality of life (QoL) assessed by EORTC QLQ-30 and QLQ-BN20
Timepoint [3] 411338 0
Baseline, and then 6, 4, 9, 18 and 36 months after final TMZ dose
Secondary outcome [4] 413632 0
Change in performance status assessed by Karnofsky performance score
Timepoint [4] 413632 0
Baseline, and then 6, 4, 9, 18 and 36 months after final TMZ dose

Eligibility
Key inclusion criteria
Patients with histologically confirmed glioblastoma who have completed surgery (biopsy or debulking) and chemoradiotherapy or who have had radiotherapy alone, and have a good performance status with a Karnofsky score of at least 60.
Note the chemotherapy treatment is temozolomide (TMZ).
Minimum age
16 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Are unable to provide informed consent
2. Are unable to swallow tablets and capsules
3. Have persistent platelet count of less than 100/µL
4. Have not completed surgery and first cycle of TMZ concomitant with radiotherapy
5. Require on-going treatment with medications that increase renin levels, such as calcium channel blockers and diuretics
6. Are not motivated including those who are non-adherent, e.g., abuse alcohol
7. Less than 16 years
8. Older than 80 years
9. On other studies or trials
10. Have contraindications to any of the study treatments including asthma, systolic blood pressure (BP) less than or equal to 100mmHg, allergies to the trial medications, medications that interfere with the proposed treatments
11. Have significant immune compromise including HIV infection, organ transplant patients on immunosuppression, chronic lymphocytic leukaemia
12. Breastfeeding, pregnant or plan to be pregnant
13. Have terminal organ failure:
a. Moderate or severe renal impairment (GFR less than 60mL/min)
b. Liver disease
c. Congestive heart failure/myocardial infarction within the last 6 months.
d. Cerebrovascular disease (CVA/TIA/hemiplegia, except mild dementia).
e. Moderate or severe peripheral vascular disease.
14. Have a second cancer that is expected to impact on the results of this study.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
For the primary outcome of survival time from diagnosis, assuming exponential distribution of survival times a sample size of 75 patients will provide a 95% confidence interval of +/- 4 months for the overall median survival time. This assumes 30% censoring.

The data will be analysed using survival analysis methods (Kaplan-Meier survival curves and Cox’s proportional hazards model) so that all patients (whether or not they have died) will provide information for the estimation of overall median survival time. Analysis of both survival time from diagnosis and survival time from initiation of the intervention will be examined. The analysis of tumour progression (tumour volume and avidity) measured by FET-PET, will use non-parametric methods, as will the analysis of change in QoL. Graphical methods (plots of mean QoL score and their 95% confidence intervals) will be used to describe the changes over time. Analysis will be stratified according to IDH genotype and MGMT methylation, however, subgroup analysis will not be possible due to sample size.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/02/2023
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment outside Australia
Country [1] 24855 0
New Zealand
State/province [1] 24855 0

Funding & Sponsors
Funding source category [1] 311720 0
Charities/Societies/Foundations
Name [1] 311720 0
Gillies McIndoe Research Institute
Country [1] 311720 0
New Zealand
Primary sponsor type
Charities/Societies/Foundations
Name
Gillies McIndoe Research Institute
Address
Physical; 7 Hospital Road, Newtown, Wellington 6021
Postal: PO Box 7184, Newtown, Wellington 6242
Country
New Zealand
Secondary sponsor category [1] 313195 0
None
Name [1] 313195 0
Address [1] 313195 0
Country [1] 313195 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311171 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 311171 0
Ethics committee country [1] 311171 0
New Zealand
Date submitted for ethics approval [1] 311171 0
27/07/2021
Approval date [1] 311171 0
28/10/2021
Ethics approval number [1] 311171 0
21/CEN/203

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120202 0
Dr Swee Tan
Address 120202 0
Postal Address
Gillies McIndoe Research Institute
PO Box 7184, Newtown, Wellington 6242

Physical Address
Gillies McIndoe Research Institute
7 Hospital Road, Newtown, Wellington 6021
Country 120202 0
New Zealand
Phone 120202 0
+64 21 631 000
Fax 120202 0
Email 120202 0
swee.tan@gmri.org.nz
Contact person for public queries
Name 120203 0
Ruth Watson-Black
Address 120203 0
Postal Address
Gillies McIndoe Research Institute
PO Box 7184, Newtown, Wellington 6242

Physical Address
Gillies McIndoe Research Institute
7 Hospital Road, Newtown, Wellington 6021
Country 120203 0
New Zealand
Phone 120203 0
+64 4 282 0366
Fax 120203 0
Email 120203 0
research.nurse@gmri.org.nz
Contact person for scientific queries
Name 120204 0
Swee Tan
Address 120204 0
Postal Address
Gillies McIndoe Research Institute
PO Box 7184, Newtown, Wellington 6242

Physical Address
Gillies McIndoe Research Institute
7 Hospital Road, Newtown, Wellington 6021
Country 120204 0
New Zealand
Phone 120204 0
+64 4 282 0366
Fax 120204 0
Email 120204 0
swee.tan@gmri.org.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified data collected during the trial will be shared.
When will data be available (start and end dates)?
Data will be available after publication of the outcomes (and any protection of IP). No specific end date of when data will be shared has been decided as yet.
Available to whom?
Researchers in glioblastoma.
Available for what types of analyses?
No restrictions on analyses are predicted.
How or where can data be obtained?
Requests are made to the Principal Investigator via email or website;
www.gmri.org or swee.tan@gmri.org.nz


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
16507Ethical approval  research.nurse@gmri.org.nz 384286-(Uploaded-06-09-2022-10-46-48)-Study-related document.pdf
17089OtherSCOTT approval letter research.nurse@gmri.org.nz SCOTT approval 384286-(Uploaded-06-09-2022-10-45-33)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.