Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001054606
Ethics application status
Approved
Date submitted
20/08/2014
Date registered
2/10/2014
Date last updated
30/03/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pilot study to evaluate the prognostic and metabolic effects of metformin during treatment of metastatic prostate cancer with androgen deprivation therapy
Scientific title
Pilot study to evaluate the prognostic and metabolic effects of metformin during treatment of metastatic prostate cancer with androgen deprivation therapy
Secondary ID [1] 284884 0
Nil
Universal Trial Number (UTN)
Trial acronym
ADMET – ADjuvant METformin in metastatic prostate cancer with ADT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic prostate cancer 292322 0
Condition category
Condition code
Cancer 292658 292658 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two-arm study. Both Arm 1 and Arm 2 will be receiving androgen deprivation therapy (ADT). The ADT used is a combined androgen blockade with luteinizing hormone releasing hormone (LHRH) agonist (45mg EligardTrademark) and AR antagonist (50mg Cosudex/bicalutamide) for the first 4 weeks as per standard of care. After that, EligardTrademark will continue as monotherapy 6 monthly unless clinically indicated for complete androgen blockade. At 12 weeks into ADT, participants will receive 1500mg metformin (3x500mg daily, with meals) or placebo depending on the treatment arm allocated after randomization.

Metformin or Placebo tablets will be dispensed every 12 weeks. Participants will need to return the unused tablets to the research team before or after each dispensing for drug accountability purpose. Moreover, participants will have 6 weekly medical review.

Arm 1
Metformin hydrochloride 500mg tablet
Dosage: 1500mg daily
Duration: 30 weeks
Mode of administration: Oral
Intervention code [1] 289693 0
Treatment: Drugs
Comparator / control treatment
Arm 2
Placebo
Duration: 30 weeks
Mode of administration: Oral

The placebo are biconvex, film coated tablets. They have everything the same as the Metformin tablet except without active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 292505 0
Time to progression of disease defined as biochemical, radiographic or clinical progression
Timepoint [1] 292505 0
Prostate specific antigen and 6 weekly clincial review will be used to determine biochemical and clinical progression: every 6 weeks for 42 weeks and at week 54 (end-of-study visit)

CT scan and bone scan will be used to determine radiographic progression: if clinically indicated. Radiographically, Prostate Cancer Working Group (PCWG) 2 criteria will be used.
Secondary outcome [1] 309114 0
Changes to metabolic parameters including fasting insulin by blood test , fasting glucose by blood test, body mass index, and serum biomarkers (Leptin, adiponectin, ghrelin)
Timepoint [1] 309114 0
Every 6 weeks for 42 weeks and at week 54 (end-of-study visit)
Secondary outcome [2] 310671 0
Molecular changes to the circulating tumour cells.
Circulating tumour cells will be isolated using Stemcell Technology RosetteSep. The isolated cells will be lysed. The chages will be assessed by real-time polymerase chain reaction.
Timepoint [2] 310671 0
Every 12 weeks for 36 weeks and at week 54 (End-of-Study Visit)

Eligibility
Key inclusion criteria
1. Age above 18 years
2. Competent to understand information and provide written informed consent
3. Metastatic prostate adenocarcinoma defined by radiological diagnosis (TNM staging), PSA greater or than equal to 20 in the presence of tissue diagnosis or abnormal prostate examination, PSA recurrence post surgery or radiotherapy
4. No prior chemotherapy for prostate cancer
5. Not on insulin control medications [Insulin, oral hypoglycaemic agents, systemic corticosteroid of any dosage, atypical antipsychotic drugs of any dose]
6. Adequate renal function (Creatinine equal to 177mmol/L, GFR greater than 30 mls/min)
7. Adequate hepatic function (Bilirubin must be equal to 1.5 x upper limit of normal range, ALT and ALP must be equal to 2.5 x upper limit of normal)
8. Life expectancy greater than 6 months
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
1. Known brain metastasis
2. Malignant disease other than prostate cancer at the time of enrolment, apart from completely treated non-melanomatous skin malignancy
3. Prior chemotherapy for prostate cancer
4. Prior primary radiotherapy within 6 weeks
5. Previously treated with ketoconazole for greater than 7 days
6. Prior systemic treatment with an azole drug within 4 weeks
7. Prior antiandrogen treatment within 6 weeks
8. History of lactic acidosis
9. History of pituitary or adrenal dysfunction
10. Cardiac (heart failure NYHA class II or greater, acute myocardial infarct, unstable angina, arterial-thromboembolic event within past 6 months) or respiratory insufficiency (active pulmonary embolism, severe chronic obstructive pulmondary disease), severe liver failure (cirrhosis with a Child-Pugh level of B or greater), severe infection that is likely to increase the risk of lactic acidosis
11. Medical or psychiatric conditions that compromise the patient's ability to give informed consent
12. History of pituitary or adrenal dysfunction
13. Participants will be discharged from the study if unable to tolerate metformin due to adverse reactions or develop medical conditions such as renal failure or diabetes requiring additional agents other than metformin

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Enrolment: Consecutive patients with metastatic prostate cancer suitable for trial who has been referred to service areas of Princess Alexandra Hospital
Randomization: Central randomisation by computer to treatment groups
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Central randomisation by computer
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Nil
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/09/2014
Actual
8/09/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 2682 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 3795 0
Epworth Richmond - Richmond
Recruitment hospital [3] 5682 0
Gold Coast Hospital - Southport
Recruitment postcode(s) [1] 8377 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 9684 0
3121 - Richmond

Funding & Sponsors
Funding source category [1] 289508 0
Hospital
Name [1] 289508 0
2014 Princess Alexandra Hospital Research Support Scheme Grants
Country [1] 289508 0
Australia
Funding source category [2] 289808 0
Commercial sector/Industry
Name [2] 289808 0
Tolmar Australia Pty Ltd
Country [2] 289808 0
Australia
Primary sponsor type
University
Name
Queensland University of Technology
Address
2, George Street, Brisbane, QLD 4122, Australia
Country
Australia
Secondary sponsor category [1] 288189 0
None
Name [1] 288189 0
Address [1] 288189 0
Country [1] 288189 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291253 0
Metro South Health service District Human Research Ethics Committee
Ethics committee address [1] 291253 0
Princess Alexandra Hospital, Centres for Health Research, Level 7, Translational Research Institute, 37 Kent Street, Woolloongabba QLD 4102
Ethics committee country [1] 291253 0
Australia
Date submitted for ethics approval [1] 291253 0
Approval date [1] 291253 0
19/05/2014
Ethics approval number [1] 291253 0
EC00167
Ethics committee name [2] 291254 0
Queensland University of Technology Human Research Ethics Committee
Ethics committee address [2] 291254 0
Research Ethics Unit, Office of Research, Level 4, 88 Musk Ave, QUT Kelvin Grove QLD 4059
Ethics committee country [2] 291254 0
Australia
Date submitted for ethics approval [2] 291254 0
Approval date [2] 291254 0
29/07/2014
Ethics approval number [2] 291254 0
EC00171
Ethics committee name [3] 292842 0
Epworth HealthCare Human Research Ethics Committee
Ethics committee address [3] 292842 0
89 Bridge Road, Richmond VIC 3121
Ethics committee country [3] 292842 0
Australia
Date submitted for ethics approval [3] 292842 0
Approval date [3] 292842 0
24/04/2015
Ethics approval number [3] 292842 0
EC00217

Summary
Brief summary
This study will investigate the effects of combining metformin with androgen deprivation therapy (ADT) in men with metastatic prostate cancer.

You may be eligible to join this study if you are male, aged 18 years or above and have been diagnosed with metastatic prostate adenocarcinoma, for which you have not received any ADT.

Study details
Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will take 3 x 500mg oral tablets of metformin hydrochloride daily for 30 weeks, whilst participants in the other group will take 3 oral tablets of placebo (inactive treatment) daily for 30 weeks.
Participants will be followed-up every 6 weeks for 54 weeks, in order to determine metabolic and tumour responses and tumour progression.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49410 0
Prof Colleen Nelson
Address 49410 0
Australian Prostate Cancer Research Centre – Queensland
Level 1, Building 1, Princess Alexandra Hospital, 199 Ipswich Road, Brisbane QLD 4102
Country 49410 0
Australia
Phone 49410 0
+61 7 3176 7443
Fax 49410 0
Email 49410 0
[email protected]
Contact person for public queries
Name 49411 0
Colleen Nelson
Address 49411 0
Australian Prostate Cancer Research Centre – Queensland
Level 1, Building 1, Princess Alexandra Hospital, 199 Ipswich Road, Brisbane QLD 4102
Country 49411 0
Australia
Phone 49411 0
+61 7 3176 7443
Fax 49411 0
Email 49411 0
[email protected]
Contact person for scientific queries
Name 49412 0
Colleen Nelson
Address 49412 0
Australian Prostate Cancer Research Centre – Queensland
Level 1, Building 1, Princess Alexandra Hospital, 199 Ipswich Road, Brisbane QLD 4102
Country 49412 0
Australia
Phone 49412 0
+61 7 3176 7443
Fax 49412 0
Email 49412 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
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