Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12606000301561
Ethics application status
Approved
Date submitted
28/07/2004
Date registered
28/07/2004
Date last updated
12/11/2018
Date data sharing statement initially provided
12/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
TOAD - Timing of androgen deprivation intervention in prostate cancer patients with a rising PSA
Scientific title
A collaborative randomised phase III trial: The timing Of intervention with Androgen Deprivation in prostate cancer patients with a rising Prostate Specific Antigen (PSA)
Secondary ID [1] 79 0
VCOG PR 1-03
Secondary ID [2] 80 0
TROG 03.06
Secondary ID [3] 81 0
National Clinical Trials Registry: NCTR580
Secondary ID [4] 279 0
Trans-Tasman Radiation Oncology Group Inc (TROG): TROG 03.06
Universal Trial Number (UTN)
Trial acronym
TOAD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostate cancer 52 0
Condition category
Condition code
Cancer 58 58 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will be randomised to receive androgen deprivation therapy either immediately (experimental arm)
Intervention code [1] 1195 0
Treatment: Other
Comparator / control treatment
Patients will be randomised to receive androgen deprivation therapy delayed for at least 2 years or until evidence of significant disease progression (control arm).
Control group
Active

Outcomes
Primary outcome [1] 1855 0
The primary endpoint of the trial is death from any cause
Timepoint [1] 1855 0
Measured at 6 monthly assessments
Secondary outcome [1] 3267 0
Cancer specific survival
Timepoint [1] 3267 0
6 monthly for 5 years
Secondary outcome [2] 3268 0
Clinical progression
Timepoint [2] 3268 0
6 monthly for 5 years
Secondary outcome [3] 3269 0
Time to first androgen independence
Timepoint [3] 3269 0
6 monthly for 5 years
Secondary outcome [4] 3270 0
Complication rate incidence and timing (eg cord compression, pathological fracture)
Timepoint [4] 3270 0
6 monthly for 5 years
Secondary outcome [5] 3271 0
Treatment related morbidity (including cognitive, osteoporosis)
Timepoint [5] 3271 0
6 monthly for 5 years
Secondary outcome [6] 3272 0
Quality of life
Timepoint [6] 3272 0
6 monthly for 5 years
Secondary outcome [7] 3273 0
Prognostic factors for progression (delayed group)
Timepoint [7] 3273 0
6 monthly for 5 years

Eligibility
Key inclusion criteria
STUDIES 1 AND 2- Histologically confirmed adenocarcinoma of the prostate- Accessible for follow-up- Informed consent to be randomised to immediate or delayed androgen deprivation- Males aged 18 years and overINCLUSION CRITERIA STUDY 1 PSA relapse after definitive radical treatment- No evidence of metastatic disease on staging investigations (bone scan, abdomino-pelvic CT scan)- Prior androgen deprivation limited to a maximum of seven months neo-adjuvant/concurrent treatment, completed at least 12 months prior to study entryINCLUSION CRITERIA STUDY 2- Not suitable for radical treatment at primary diagnosis.- Decision not to treat curatively- No symptoms due to local or metastatic disease requiring radiation or immediate hormone therapy- No prior androgen deprivation therapy
Minimum age
18 Years
Maximum age
Not stated
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Significant co-morbidity limiting life expectancy to less than 5 years- Patients with symptomatic disease requiring therapy- Previous androgen deprivation for longer than 7 months (Study 1)- Diagnosis of PSA relapse or incurable disease more than six months prior to randomisation- Patients entered into TROG studies 96.01 or RADAR- Patients with a PSA doubling time of less than 3 months (Study 1)

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)
Randomisation is performed centrally using computer software.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment is allocated using a database embedded dynamically balanced randomisation method.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2004
Actual
3/09/2004
Date of last participant enrolment
Anticipated
Actual
13/07/2012
Date of last data collection
Anticipated
Actual
31/12/2013
Sample size
Target
750
Accrual to date
Final
293
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 87 0
Government body
Name [1] 87 0
National Health & Medical Research Council
Country [1] 87 0
Australia
Funding source category [2] 88 0
Commercial sector/Industry
Name [2] 88 0
untied pharmaceutical company grants
Country [2] 88 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
The Cancer Council Victoria
Address
1 Rathdowne St, Carlton South, 3053, VIC
Country
Australia
Secondary sponsor category [1] 68 0
Other Collaborative groups
Name [1] 68 0
Trans Tasman Radiation Oncology Group (TROG)
Address [1] 68 0
Dept of Radiation Oncology
Newcastle Mater Misericordiae Hospital
Locked Bag7, NHMRC NSW 2310
Country [1] 68 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 769 0
Alfred Hospital
Ethics committee address [1] 769 0
Ethics committee country [1] 769 0
Australia
Date submitted for ethics approval [1] 769 0
Approval date [1] 769 0
25/10/2004
Ethics approval number [1] 769 0
Ethics committee name [2] 770 0
Campbelltown Hospital
Ethics committee address [2] 770 0
Ethics committee country [2] 770 0
Australia
Date submitted for ethics approval [2] 770 0
Approval date [2] 770 0
06/12/2005
Ethics approval number [2] 770 0
Ethics committee name [3] 771 0
Cham, Mr Chee Wee
Ethics committee address [3] 771 0
Ethics committee country [3] 771 0
Australia
Date submitted for ethics approval [3] 771 0
Approval date [3] 771 0
19/08/2005
Ethics approval number [3] 771 0
Ethics committee name [4] 772 0
Christchurch Hospital
Ethics committee address [4] 772 0
Ethics committee country [4] 772 0
New Zealand
Date submitted for ethics approval [4] 772 0
Approval date [4] 772 0
19/04/2005
Ethics approval number [4] 772 0
Ethics committee name [5] 773 0
Ethics committee address [5] 773 0
Ethics committee country [5] 773 0
Australia
Date submitted for ethics approval [5] 773 0
Approval date [5] 773 0
Ethics approval number [5] 773 0
Ethics committee name [6] 774 0
Concord Repatriation Hosp
Ethics committee address [6] 774 0
Ethics committee country [6] 774 0
Australia
Date submitted for ethics approval [6] 774 0
Approval date [6] 774 0
05/10/2004
Ethics approval number [6] 774 0
Ethics committee name [7] 775 0
Dunedin Hospital
Ethics committee address [7] 775 0
Ethics committee country [7] 775 0
New Zealand
Date submitted for ethics approval [7] 775 0
Approval date [7] 775 0
24/06/2005
Ethics approval number [7] 775 0
Ethics committee name [8] 776 0
East Coast Cancer Centre
Ethics committee address [8] 776 0
Ethics committee country [8] 776 0
Australia
Date submitted for ethics approval [8] 776 0
Approval date [8] 776 0
30/11/2004
Ethics approval number [8] 776 0
Ethics committee name [9] 777 0
Geelong Hospital
Ethics committee address [9] 777 0
Ethics committee country [9] 777 0
Australia
Date submitted for ethics approval [9] 777 0
Approval date [9] 777 0
04/11/2004
Ethics approval number [9] 777 0
Ethics committee name [10] 778 0
Ethics committee address [10] 778 0
Ethics committee country [10] 778 0
Australia
Date submitted for ethics approval [10] 778 0
Approval date [10] 778 0
28/04/2006
Ethics approval number [10] 778 0
Ethics committee name [11] 779 0
Liverpool Hospital
Ethics committee address [11] 779 0
Ethics committee country [11] 779 0
Australia
Date submitted for ethics approval [11] 779 0
Approval date [11] 779 0
06/11/2004
Ethics approval number [11] 779 0
Ethics committee name [12] 780 0
Mander, Mr Julian
Ethics committee address [12] 780 0
Ethics committee country [12] 780 0
Australia
Date submitted for ethics approval [12] 780 0
Approval date [12] 780 0
19/05/2006
Ethics approval number [12] 780 0
Ethics committee name [13] 781 0
Mater QRI
Ethics committee address [13] 781 0
Ethics committee country [13] 781 0
Australia
Date submitted for ethics approval [13] 781 0
Approval date [13] 781 0
09/09/2004
Ethics approval number [13] 781 0
Ethics committee name [14] 782 0
Monash Medical Centre
Ethics committee address [14] 782 0
Ethics committee country [14] 782 0
Australia
Date submitted for ethics approval [14] 782 0
Approval date [14] 782 0
19/04/2006
Ethics approval number [14] 782 0
Ethics committee name [15] 783 0
Nepean Cancer Care Centre
Ethics committee address [15] 783 0
Ethics committee country [15] 783 0
Australia
Date submitted for ethics approval [15] 783 0
Approval date [15] 783 0
29/03/2005
Ethics approval number [15] 783 0
Ethics committee name [16] 784 0
Newcastle Mater
Ethics committee address [16] 784 0
Ethics committee country [16] 784 0
Australia
Date submitted for ethics approval [16] 784 0
Approval date [16] 784 0
18/03/2005
Ethics approval number [16] 784 0
Ethics committee name [17] 785 0
Peter MacCallum Cancer Centre
Ethics committee address [17] 785 0
Ethics committee country [17] 785 0
Australia
Date submitted for ethics approval [17] 785 0
Approval date [17] 785 0
24/08/2004
Ethics approval number [17] 785 0
Ethics committee name [18] 786 0
Princess Alexandra Hospital
Ethics committee address [18] 786 0
Ethics committee country [18] 786 0
Australia
Date submitted for ethics approval [18] 786 0
Approval date [18] 786 0
30/08/2004
Ethics approval number [18] 786 0
Ethics committee name [19] 787 0
Ethics committee address [19] 787 0
Ethics committee country [19] 787 0
Australia
Date submitted for ethics approval [19] 787 0
Approval date [19] 787 0
Ethics approval number [19] 787 0
Ethics committee name [20] 788 0
Repatriation General Hospital
Ethics committee address [20] 788 0
Ethics committee country [20] 788 0
Australia
Date submitted for ethics approval [20] 788 0
Approval date [20] 788 0
04/08/2004
Ethics approval number [20] 788 0
Ethics committee name [21] 789 0
Royal Brisbane Hospital
Ethics committee address [21] 789 0
Ethics committee country [21] 789 0
Australia
Date submitted for ethics approval [21] 789 0
Approval date [21] 789 0
03/08/2004
Ethics approval number [21] 789 0
Ethics committee name [22] 790 0
Royal Prince Alfred
Ethics committee address [22] 790 0
Ethics committee country [22] 790 0
Australia
Date submitted for ethics approval [22] 790 0
Approval date [22] 790 0
23/08/2004
Ethics approval number [22] 790 0
Ethics committee name [23] 791 0
Sinclair, Mr Graham
Ethics committee address [23] 791 0
Ethics committee country [23] 791 0
Australia
Date submitted for ethics approval [23] 791 0
Approval date [23] 791 0
28/06/2005
Ethics approval number [23] 791 0
Ethics committee name [24] 792 0
Sir Charles Gairdner Hospital
Ethics committee address [24] 792 0
Ethics committee country [24] 792 0
Australia
Date submitted for ethics approval [24] 792 0
Approval date [24] 792 0
19/12/2005
Ethics approval number [24] 792 0
Ethics committee name [25] 793 0
Syme, Mr Rodney
Ethics committee address [25] 793 0
Ethics committee country [25] 793 0
Australia
Date submitted for ethics approval [25] 793 0
Approval date [25] 793 0
01/03/2005
Ethics approval number [25] 793 0
Ethics committee name [26] 794 0
St George Hospital
Ethics committee address [26] 794 0
Ethics committee country [26] 794 0
Australia
Date submitted for ethics approval [26] 794 0
Approval date [26] 794 0
16/03/2005
Ethics approval number [26] 794 0
Ethics committee name [27] 795 0
Vivian, Mr Justin
Ethics committee address [27] 795 0
Ethics committee country [27] 795 0
Australia
Date submitted for ethics approval [27] 795 0
Approval date [27] 795 0
19/05/2006
Ethics approval number [27] 795 0
Ethics committee name [28] 796 0
Waikato Hospital
Ethics committee address [28] 796 0
Ethics committee country [28] 796 0
New Zealand
Date submitted for ethics approval [28] 796 0
Approval date [28] 796 0
23/11/2004
Ethics approval number [28] 796 0
Ethics committee name [29] 797 0
Wellington Hospital
Ethics committee address [29] 797 0
Ethics committee country [29] 797 0
New Zealand
Date submitted for ethics approval [29] 797 0
Approval date [29] 797 0
Ethics approval number [29] 797 0
Ethics committee name [30] 798 0
Ethics committee address [30] 798 0
Ethics committee country [30] 798 0
Australia
Date submitted for ethics approval [30] 798 0
Approval date [30] 798 0
06/08/2004
Ethics approval number [30] 798 0
Ethics committee name [31] 799 0
Westmead Hospital
Ethics committee address [31] 799 0
Ethics committee country [31] 799 0
Australia
Date submitted for ethics approval [31] 799 0
Approval date [31] 799 0
26/10/2004
Ethics approval number [31] 799 0
Ethics committee name [32] 6163 0
Auckland City Hospital
Ethics committee address [32] 6163 0
Waikato DHB, Regional Cancer Centre, Private Bag, 3200 Hamilton, NZ
Ethics committee country [32] 6163 0
New Zealand
Date submitted for ethics approval [32] 6163 0
26/10/2006
Approval date [32] 6163 0
26/10/2006
Ethics approval number [32] 6163 0
WAI/04/07/058
Ethics committee name [33] 6164 0
Royal North Shore Hospital
Ethics committee address [33] 6164 0
Research Office, Level 4, Vindin House, RNSH, Pacific Hwy, St Leonards, NSW 2065
Ethics committee country [33] 6164 0
Australia
Date submitted for ethics approval [33] 6164 0
16/09/2006
Approval date [33] 6164 0
16/09/2006
Ethics approval number [33] 6164 0
0608-144M
Ethics committee name [34] 6165 0
Dr Henry Woo
Ethics committee address [34] 6165 0
New South Wales Cancer Council
Ethics committee country [34] 6165 0
Australia
Date submitted for ethics approval [34] 6165 0
10/01/2005
Approval date [34] 6165 0
10/01/2005
Ethics approval number [34] 6165 0
123
Ethics committee name [35] 6166 0
Illawarra Cancer Care Centre
Ethics committee address [35] 6166 0
SE Sydney and Illawarra Area Health Service Health and Medical HREC
Ethics committee country [35] 6166 0
Australia
Date submitted for ethics approval [35] 6166 0
14/05/2008
Approval date [35] 6166 0
14/05/2008
Ethics approval number [35] 6166 0
CT08/001

Summary
Brief summary
This is a clinical trial for patients with prostate cancer. The aim of the project is to provide information about the best timing to start treatment in men who have a rising PSA (prostate specific antigen) blood test, after having had treatment with the aim of curing their prostate cancer. In some men, the surgery or radiotherapy given initially in the attempt to cure the cancer is not successful. One of the earliest ways of detecting recurrence of the cancer in these men is with the PSA blood test, which can detect activity of the cancer months or years before other tests, and usually long before any symptoms appear.
We know that treatment with hormone therapy – removing the male hormone testosterone – is helpful in controlling advanced disease causing symptoms, although it is not a cure. This is called ‘androgen deprivation’, testosterone being an androgen hormone. The cancer cells are deprived of a source of energy, keeping them under control for a while, but eventually they tend to start growing again in spite of the treatment. We know that using androgen deprivation usually causes the PSA level in men to fall, including men in your situation who have no other signs of active cancer. What we do not know is whether using androgen deprivation immediately the PSA starts to rise will prolong life more than waiting to start treatment until there are other signs that the disease is progressing.
It would be simple to start everyone on treatment with androgen deprivation if there were no side effects with the treatment. However, there are a number of side effects that may interfere with day-to-day living. These include (but are not limited to): hot flushes, tiredness, anaemia, and loss of muscle mass and bone density. There may be weight gain, and nipple tenderness or swelling. Some men notice changes in mental function, or shortness of breath. Most also find that sex drive and erectile function, if normal before starting treatment, cease. Quality of life may be affected. If androgen deprivation therapy is ceased, some of the side effects (such as loss of sex drive, loss of muscle bulk or bone mineral density) may be halted or reversed. Generally the standard approach would be to delay introducing treatment until the disease progresses.
So the purpose of the study is to see whether immediate treatment is better or worse than delayed treatment in terms of prolonging lifespan, balanced against the effects on the quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35547 0
Address 35547 0
Country 35547 0
Phone 35547 0
Fax 35547 0
Email 35547 0
Contact person for public queries
Name 10384 0
Deborah Howell
Address 10384 0
The Cancer Council Victoria
1 Rathdowne Street
Carlton VIC 3053
Country 10384 0
Australia
Phone 10384 0
+61(0)3 9635 5179
Fax 10384 0
+61(0)3 9635 5410
Email 10384 0
[email protected]
Contact person for scientific queries
Name 1312 0
Prof Gillian Duchesne
Address 1312 0
Director Radiation Oncology
Peter MacCallum Cancer Centre
Locked Bag 1
A'Beckett Street
Melbourne Victoria 8001
Country 1312 0
Australia
Phone 1312 0
+61(0)3 9656 1004
Fax 1312 0
+61(0)3 9656 1424
Email 1312 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
EmbaseTiming of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.2016https://dx.doi.org/10.1016/S1470-2045%2816%2900107-8
EmbaseHealth-related quality of life for immediate versus delayed androgen-deprivation therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.2017https://dx.doi.org/10.1016/S1470-2045%2817%2930426-6
N.B. These documents automatically identified may not have been verified by the study sponsor.