Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00193856
Status:
COMPLETED
Last Update Posted:
2017-10-12
First Post:
2005-09-12
Brief Title:
RADAR Trial - Randomised Androgen Deprivation and Radiotherapy
Sponsor:
Trans Tasman Radiation Oncology Group
Organization:
Trans Tasman Radiation Oncology Group
Study Overview
Official Title:
A Randomised Trial Investigating the Effect on Biochemical PSA Control and Survival of Different Durations of Adjuvant Androgen Deprivation in Association With Definitive Radiation Treatment for Localised Carcinoma of the Prostate
Status:
COMPLETED
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The principal objectives of the RADAR trial is to address the hypotheses 1 that 18 months androgen deprivation in conjunction with radiotherapy is superior to 6 months androgen deprivation prior to and during radiotherapy 2 that 18 months Bisphosphonate therapy will prevent bone loss caused by androgen deprivation therapy and further reduce relapse risk by impeding the development of bony metastases
Detailed Description:
Traditionally androgen deprivation by orchidectomy or more recently by medication has been reserved for the palliative treatment of men with advanced incurable prostate cancer However evidence from large scale trials is beginning to suggest that androgen deprivation AD may be helpful in preventing relapse in patients with more localised disease who are treated surgically or by radiotherapy Of the 8000 patients per annum who are treated with curative intent one half 4000 have cancers where adjuvant AD may be prescribed according to interpretation of the registered indications There are however enormous variations in prescribing practices which reflect uncertainty as to the appropriate indications An important issue is osteopenia
The increasing use of AD in men with earlier stages of cancer whose life expectancies exceed 3 years has exposed many unwanted metabolic sequelae of prolonged AD the most important being osteopenia In 1996 with the funding support of the NHMRC and the pharmaceutical industry TROG therefore launched a large randomised three-arm trial Two of the arms repeated the two arms of the US Radiation Therapy Oncology Group RTOG 8601 trial which at the time was showing early indications of benefit for the addition of two months maximal androgen deprivation MAD using Goserelin Zoladex and Flutamide before radiation therapy and one month during Since work from Canada had indicated that continued AD for periods longer than three months produced additional shrinkage of the prostatic tumour the TROG 9601 trial incorporated a third arm six months MAD prior to and during radiotherapy The trial completed its recruitment target of 800 eligible patients in early 2000 Although in August 2001 the median follow up time was still very short a preliminary analysis indicated that significant increases in time to biochemical relapse had been produced by AD In fact the benefits of AD were independent of stage tumour grade and initial PSA value which were confirmed also to predict time to biochemical failure The hazard of relapse reduced to 075 055 - 097 95 confidence intervals with 3 months AD and still further to 06 045 - 082 with six months AD
Subsequent international developments in this area of research encouraged the design of a follow on trial A European Organisation for Research and Treatment of Cancer EORTC trial reported that 3 years of adjuvant post hoc AD using Goserelin alone administered after radiotherapy reduced relapse and improved survival in patients with locally advanced prostate cancer The US Radiation Therapy Oncology Group RTOG 8531 trial indicated that indefinite Goserelin administration after radiotherapy reduced treatment failure rates at all sites when compared with radiotherapy alone The RTOG 9202 trial showed that 24 months of adjuvant Goserelin also reduced failure rates in patients treated with 4 months of MAD prior to and during radiotherapy Subset analyses of the RTOG trials suggested that patients who gain most from prolonged AD in terms of survival are those with high grade cancers
It was therefore logical for TROG to propose a second trial with the intention of finding out whether an additional 12 months of AD administered after radiotherapy aka intermediate term AD ITAD would reduce relapse and mortality in patients treated with six months of AD prior to and during radiotherapy aka short term AD STAD as in the best arm of its first 9601 trial The availability of the potent bisphosphonate zoledronic acid also made it possible to find out whether or not osteopenia induced in the two arms of the proposed second trial would be prevented by a second random assignment to 18 months bisphosphonate therapy BP
This is a randomised phase III multicentre clinical trial
After informed consent is given and eligibility is checked patients will be randomised to one of four trial arms
1 6 months of androgen blockade with an LH-RH analogue 5 months before start of radiotherapy STAD
2 18 months of androgen blockade with an LH-RH analogue starting 5 months before start of radiotherapy ITAD
3 18 months of therapy with zoledronic acid 4 mg by intravenous infusion every 3 months for 18 months beginning concurrently with STAD
4 18 months of therapy with zoledronic acid beginning concurrently with ITAD
Stratification will be according to the following criteria
T2 T3 4 Gleason score 2 - 6 7 Presenting PSA 10 10 - 20 20 Treatment centre
Radiation Treatment will be delivered using a conventional technique unless the treatment centre of the participating clinician demonstrates an ability to deliver the treatment using a CRT IMRT or HDRB technique verified by the trial TACT
Drug Treatment
LH-RH analogue LH-RHa Leuprorelin acetate 225 mg will be delivered as a depot injection every 3 months This will be administered as an Intramuscular injection IMI
Zoledronic acid 4 mg will be delivered as an intravenous infusion over 15 minutes once every 3 months for 18 months in patients randomised to this therapy No placebo therapy will be given to patients randomised to no bisphosphonate therapy treatment arm
The increasing use of AD in men with earlier stages of cancer whose life expectancies exceed 3 years has exposed many unwanted metabolic sequelae of prolonged AD the most important being osteopenia In 1996 with the funding support of the NHMRC and the pharmaceutical industry TROG therefore launched a large randomised three-arm trial Two of the arms repeated the two arms of the US Radiation Therapy Oncology Group RTOG 8601 trial which at the time was showing early indications of benefit for the addition of two months maximal androgen deprivation MAD using Goserelin Zoladex and Flutamide before radiation therapy and one month during Since work from Canada had indicated that continued AD for periods longer than three months produced additional shrinkage of the prostatic tumour the TROG 9601 trial incorporated a third arm six months MAD prior to and during radiotherapy The trial completed its recruitment target of 800 eligible patients in early 2000 Although in August 2001 the median follow up time was still very short a preliminary analysis indicated that significant increases in time to biochemical relapse had been produced by AD In fact the benefits of AD were independent of stage tumour grade and initial PSA value which were confirmed also to predict time to biochemical failure The hazard of relapse reduced to 075 055 - 097 95 confidence intervals with 3 months AD and still further to 06 045 - 082 with six months AD
Subsequent international developments in this area of research encouraged the design of a follow on trial A European Organisation for Research and Treatment of Cancer EORTC trial reported that 3 years of adjuvant post hoc AD using Goserelin alone administered after radiotherapy reduced relapse and improved survival in patients with locally advanced prostate cancer The US Radiation Therapy Oncology Group RTOG 8531 trial indicated that indefinite Goserelin administration after radiotherapy reduced treatment failure rates at all sites when compared with radiotherapy alone The RTOG 9202 trial showed that 24 months of adjuvant Goserelin also reduced failure rates in patients treated with 4 months of MAD prior to and during radiotherapy Subset analyses of the RTOG trials suggested that patients who gain most from prolonged AD in terms of survival are those with high grade cancers
It was therefore logical for TROG to propose a second trial with the intention of finding out whether an additional 12 months of AD administered after radiotherapy aka intermediate term AD ITAD would reduce relapse and mortality in patients treated with six months of AD prior to and during radiotherapy aka short term AD STAD as in the best arm of its first 9601 trial The availability of the potent bisphosphonate zoledronic acid also made it possible to find out whether or not osteopenia induced in the two arms of the proposed second trial would be prevented by a second random assignment to 18 months bisphosphonate therapy BP
This is a randomised phase III multicentre clinical trial
After informed consent is given and eligibility is checked patients will be randomised to one of four trial arms
1 6 months of androgen blockade with an LH-RH analogue 5 months before start of radiotherapy STAD
2 18 months of androgen blockade with an LH-RH analogue starting 5 months before start of radiotherapy ITAD
3 18 months of therapy with zoledronic acid 4 mg by intravenous infusion every 3 months for 18 months beginning concurrently with STAD
4 18 months of therapy with zoledronic acid beginning concurrently with ITAD
Stratification will be according to the following criteria
T2 T3 4 Gleason score 2 - 6 7 Presenting PSA 10 10 - 20 20 Treatment centre
Radiation Treatment will be delivered using a conventional technique unless the treatment centre of the participating clinician demonstrates an ability to deliver the treatment using a CRT IMRT or HDRB technique verified by the trial TACT
Drug Treatment
LH-RH analogue LH-RHa Leuprorelin acetate 225 mg will be delivered as a depot injection every 3 months This will be administered as an Intramuscular injection IMI
Zoledronic acid 4 mg will be delivered as an intravenous infusion over 15 minutes once every 3 months for 18 months in patients randomised to this therapy No placebo therapy will be given to patients randomised to no bisphosphonate therapy treatment arm
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| ACTRN12607000097448 | REGISTRY | Australian New Zealand Clinical Trials Registry | None |