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Prostate CancerPhase 3NCT00193856

RADAR Trial - Randomised Androgen Deprivation and Radiotherapy

A Phase 3 study testing Leuprorelin Acetate, Zoledronic Acid and Conventional external beam therapy in people with Prostate Cancer, run by Trans Tasman Radiation Oncology Group at 24 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Leuprorelin Acetate, Zoledronic Acid and Conventional external beam therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,071 participants
Where
24 sitesin 2 countries
Study dates
Oct 2003to Aug 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological confirmation of adenocarcinoma of the prostate in the three months prior to randomisation
  • Gleason primary and secondary pattern reported. If the volume of tumour in biopsies is too small for the pathologist to allocate a secondary pattern, the primary pattern alone is sufficient.
  • Primary tumour stage T2b - 4 (UICC 2002), or T2a providing biopsies demonstrate Gleason score 7 or more, and presenting PSA 10 or more
  • PSA value obtained within one month of randomisation
  • No evidence of lymphatic or haematogenous metastases, as determined by negative chest x-ray, CT scan of abdomen and pelvis, and bone scan in the 3 months prior to randomisation
  • ECOG performance status 0 - 1
Show all 9Show fewer
  • No concurrent medical conditions likely to significantly reduce prospects of 5 year survival
  • Patient accessible to follow up at intervals specified in protocol
  • Written informed consent given (signed by both patient and investigator prior to randomisation)

Who cannot join

  • Previous or concurrent malignancy within previous 5 years except for non-melanomatous skin cancer
  • Prostatectomy
  • Prior pelvic radiotherapy
  • Prior hormone treatment for prostate cancer
  • Inability to complete self administered QOL questionnaire
  • Prior bisphosphonate therapy
Show all 12Show fewer
  • Serum creatinine > 2 x ULN
  • Osteoporosis resulting in >30% loss in vertebral height in one or more thoraco-lumbar vertebrae
  • Liver disease resulting in ALT or AST levels >3 x ULN
  • Prolonged continuous glucocorticoid therapy > 10 mg/day of prednisone equivalent (>6 months)
  • Current treatment with bisphosphonate
  • Inability to attend for follow-up at the Investigator's clinic

Trial locations and contacts

24 sites in 2 countries.

24 sites in 2 countries

Australia18 sites

  • Campbelltown Hospital

    Campbelltown, New South Wales, 2560

  • Peter MacCallum Cancer Centre

    East Melbourne, Victoria, 8006

  • Andrew Love Cancer Care Centre, Geelong Hospital

    Geelong, Victoria, 3220

  • Royal Brisbane Hospital

    Herston, Queensland, 4029

  • St George Hospital

    Kogarah, New South Wales, 2217

  • Launceston General Hospital

    Launceston, Tasmania, 7250

  • Lismore Hospital

    Lismore, New South Wales, 2480

  • Liverpool Hospital

    Liverpool, New South Wales, 1871

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Calvary Mater Newcastle

    Newcastle, New South Wales, 2298

  • Nepean Cancer Care Centre

    Penrith, New South Wales, 2751

  • Mater QRI

    South Brisbane, Queensland, 4101

  • Royal North Shore Hospital

    Sydney, New South Wales, 2069

  • John Flynn Private Hospital

    Tugun, Queensland, 4224

  • Riverina Cancer Care Centre

    Wagga Wagga, New South Wales, 2650

  • Westmead Hospital

    Wentworthville, New South Wales, 2145

  • Illawarra Cancer Care Centre

    Wollongong, New South Wales

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

New Zealand6 sites

  • Auckland Hospital

    Auckland, 1001

  • Christchurch Hospital

    Christchurch, 4710

  • Dunedin Hospital

    Dunedin

  • Waikato Hospital

    Hamilton, 3200

  • Palmerston North Hospital

    Palmerston North

  • Wellington Hospital

    Wellington, 7902

Other trials in New Zealand

About this study

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.

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.

Read the 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) 86.01 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 96.01 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 0.75 (0.55 - 0.97, 95% confidence intervals) with 3 months AD, and still further to 0.6 (0.45 - 0.82) 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) 85.31 trial indicated that indefinite Goserelin administration after radiotherapy reduced treatment failure rates at all sites when compared with radiotherapy alone. The RTOG 92.02 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 (96.01) 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 22.5 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.

Conditions
Prostate Cancer
Being tested
Leuprorelin Acetate, Zoledronic Acid, Conventional external beam therapy
Keywords
Prostate Cancer, Androgen Deprivation, Hormone Therapy, RadiotherapyBisphosphonate, Prostate Specific Antigen (PSA)
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leuprorelin AcetateDrug

    LH-RH analogue (LH-RHa) (Leuprorelin acetate 22.5 mg) will be delivered as a depot injection every 3 months. This will be administered as an intramuscular injection (IMI).

  • Zoledronic AcidDrug

    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 bisphosphonate therapy.

  • Conventional external beam therapyRadiation

    The prescribed dose will be 66 Gy in 33 fractions of 2 Gy to the ICRU 50 point utilising a minimum of three fields with >= 6 MV photons.

Study groups in NCT00193856
Study groupRoleWhat they receive
AActive comparatorLH-RH analogue for 5 months prior to and during first month of radiation treatment (total 6 mths)
Receives: Drug: Leuprorelin Acetate; Radiation: Conventional external beam therapy
BActive comparatorLH-RH analogue for 5 months prior to and during first month of radiation treatment (total 6 months) + bisphosphonate therapy.
Receives: Drug: Leuprorelin Acetate; Drug: Zoledronic Acid; Radiation: Conventional external beam therapy
CExperimentalLH-RH analogue as for arm A, but continued for further 12 months (total 18 months)
Receives: Drug: Leuprorelin Acetate; Radiation: Conventional external beam therapy
DExperimentalLH-RH analogue as for arm A, but continued for further 12 months (total 18 months) + bisphosphonate therapy.
Receives: Drug: Leuprorelin Acetate; Drug: Zoledronic Acid; Radiation: Conventional external beam therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prostate cancer-specific mortality.

    Measured: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomisation of the last participant

Secondary outcomes (7)

  1. Cumulative incidence of PSA progression

    Measured: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomisation of the last participant

  2. Cumulative incidence of local, distant and bony progression and associated patterns of clinical progression

    Measured: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomisation of the last participant

  3. All-cause mortality

    Measured: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomisation of the last participant

  4. Changes in bone mineral density and osteopenic fracture

    Measured: One endpoint analysis is planned when 4.5 years have elapsed from randomisation of the last participant

  5. Quality of life assessment

    Measured: One endpoint analysis is planned when 3 years have elapsed from randomisation of the last participant

  6. Treatment related morbidity

    Measured: One endpoint analysis is planned when 4 years have elapsed from randomisation of the last participant

  7. Cumulative incidence of secondary therapeutic intervention

    Measured: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomization of the last participant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Sep 2005 (estimated)
  2. Study startOct 2003
  3. Primary completionAug 2017
  4. Study completionAug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Factorial
Masking
None (open label)
Enrolment
1,071 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00193856
Sponsor's protocol ID
TROG 03.04
Other IDs
ACTRN12607000097448
Status last verified
Oct 2017
First submitted
12 Sep 2005
Last updated
12 Oct 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Haworth A, Kearvell R, Greer PB, Hooton B, Denham JW, Lamb D, Duchesne G, Murray J, Joseph D. Assuring high quality treatment delivery in clinical trials - Results from the Trans-Tasman Radiation Oncology Group (TROG) study 03.04 "RADAR" set-up accuracy study. Radiother Oncol. 2009 Mar;90(3):299-306. doi: 10.1016/j.radonc.2008.10.011. Epub 2008 Nov 18.

    PubMed 19017549

  • Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial. Lancet Oncol. 2019 Feb;20(2):267-281. doi: 10.1016/S1470-2045(18)30757-5. Epub 2018 Dec 19.

    PubMed 30579763

  • Moulton CR, House MJ, Lye V, Tang CI, Krawiec M, Joseph DJ, Denham JW, Ebert MA. Prostate external beam radiotherapy combined with high-dose-rate brachytherapy: dose-volume parameters from deformably-registered plans correlate with late gastrointestinal complications. Radiat Oncol. 2016 Oct 31;11(1):144. doi: 10.1186/s13014-016-0719-2.

    PubMed 27799048

  • Denham JW, Steigler A, Joseph D, Lamb DS, Spry NA, Duchesne G, Atkinson C, Matthews J, Turner S, Kenny L, Tai KH, Gogna NK, Gill S, Tan H, Kearvell R, Murray J, Ebert M, Haworth A, Kennedy A, Delahunt B, Oldmeadow C, Holliday EG, Attia J. Radiation dose escalation or longer androgen suppression for locally advanced prostate cancer? Data from the TROG 03.04 RADAR trial. Radiother Oncol. 2015 Jun;115(3):301-7. doi: 10.1016/j.radonc.2015.05.016. Epub 2015 Jun 10.

    PubMed 26072289

  • Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. Lancet Oncol. 2014 Sep;15(10):1076-89. doi: 10.1016/S1470-2045(14)70328-6. Epub 2014 Aug 14.

    PubMed 25130995

  • Denham JW, Wilcox C, Joseph D, Spry NA, Lamb DS, Tai KH, Matthews J, Atkinson C, Turner S, Christie D, Gogna NK, Kenny L, Duchesne G, Delahunt B, McElduff P. Quality of life in men with locally advanced prostate cancer treated with leuprorelin and radiotherapy with or without zoledronic acid (TROG 03.04 RADAR): secondary endpoints from a randomised phase 3 factorial trial. Lancet Oncol. 2012 Dec;13(12):1260-70. doi: 10.1016/S1470-2045(12)70423-0. Epub 2012 Nov 12.

    PubMed 23151431

  • Denham JW, Wilcox C, Lamb DS, Spry NA, Duchesne G, Atkinson C, Matthews J, Turner S, Kenny L, Tai KH, Gogna NK, Ebert M, Delahunt B, McElduff P, Joseph D. Rectal and urinary dysfunction in the TROG 03.04 RADAR trial for locally advanced prostate cancer. Radiother Oncol. 2012 Nov;105(2):184-92. doi: 10.1016/j.radonc.2012.09.018. Epub 2012 Nov 3.

    PubMed 23127770

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Leuprorelin Acetate, Zoledronic Acid and Conventional external beam therapy in people with Prostate Cancer, run by Trans Tasman Radiation Oncology Group at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prostate cancer-specific mortality. (time frame: Two main endpoint analyses are planned when 6.5 and 10 years have elapsed from randomisation of the last participant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00193856, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2017.

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