RADAR Trial - Randomised Androgen Deprivation and Radiotherapy

NCT00193856 | Completed Phase 3 DMC

• 2 other identifiers: TROG 03.04ACTRN12607000097448
• Study Type: interventional
• Target: 1,071
• Locations: 2 countries
• Sites: 24

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.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; Androgen Deprivation; Hormone Therapy; RadiotherapyBisphosphonate; Prostate Specific Antigen (PSA)

Outcome Measures

Primary Outcomes (1)

• Prostate cancer-specific mortality.

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

Secondary Outcomes (7)

• Cumulative incidence of PSA progression

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

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

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

• All-cause mortality

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

• Changes in bone mineral density and osteopenic fracture

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

• Quality of life assessment

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

Study Arms (4)

A

ACTIVE COMPARATOR

LH-RH analogue for 5 months prior to and during first month of radiation treatment (total 6 mths)

Drug: Leuprorelin Acetate; Radiation: Conventional external beam therapy

B

ACTIVE COMPARATOR

LH-RH analogue for 5 months prior to and during first month of radiation treatment (total 6 months) + bisphosphonate therapy.

Drug: Leuprorelin Acetate; Drug: Zoledronic Acid; Radiation: Conventional external beam therapy

C

EXPERIMENTAL

LH-RH analogue as for arm A, but continued for further 12 months (total 18 months)

Drug: Leuprorelin Acetate; Radiation: Conventional external beam therapy

D

EXPERIMENTAL

LH-RH analogue as for arm A, but continued for further 12 months (total 18 months) + bisphosphonate therapy.

Drug: Leuprorelin Acetate; Drug: Zoledronic Acid; Radiation: Conventional external beam therapy

Interventions

Leuprorelin Acetate DRUG

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).

A; B; C; D

Zoledronic Acid DRUG

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.

B; D

Conventional external beam therapy RADIATION

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.

A; B; C; D

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Trans Tasman Radiation Oncology Group: lead
• National Health and Medical Research Council, Australia: collaborator
• Hunter Medical Research Institute (HMRI): collaborator
• Health Research Council, New Zealand: collaborator
• Novartis Pharmaceuticals: collaborator
• Cancer Society of New Zealand: collaborator
• University of Newcastle, Australia: collaborator
• Calvary Mater Newcastle, Australia: collaborator
• Maitland Cancer Appeal: collaborator
• Abbott: collaborator

Study Sites (24)

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

Lismore Hospital

Lismore, New South Wales, 2480, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 1871, Australia

Location

Calvary Mater Newcastle

Newcastle, New South Wales, 2298, Australia

Location

Nepean Cancer Care Centre

Penrith, New South Wales, 2751, Australia

Location

Royal North Shore Hospital

Sydney, New South Wales, 2069, Australia

Location

Riverina Cancer Care Centre

Wagga Wagga, New South Wales, 2650, Australia

Location

Westmead Hospital

Wentworthville, New South Wales, 2145, Australia

Location

Illawarra Cancer Care Centre

Wollongong, New South Wales, Australia

Location

Royal Brisbane Hospital

Herston, Queensland, 4029, Australia

Location

Mater QRI

South Brisbane, Queensland, 4101, Australia

Location

John Flynn Private Hospital

Tugun, Queensland, 4224, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 8006, Australia

Location

Andrew Love Cancer Care Centre, Geelong Hospital

Geelong, Victoria, 3220, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Auckland Hospital

Auckland, 1001, New Zealand

Location

Christchurch Hospital

Christchurch, 4710, New Zealand

Location

Dunedin Hospital

Dunedin, New Zealand

Location

Waikato Hospital

Hamilton, 3200, New Zealand

Location

Palmerston North Hospital

Palmerston North, New Zealand

Location

Wellington Hospital

Wellington, 7902, New Zealand

Location

Related Publications (7)

• 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.

  PMID: 19017549 RESULT

• 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.

  PMID: 30579763 DERIVED

• 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.

  PMID: 27799048 DERIVED

• 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.

  PMID: 26072289 DERIVED

• 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.

  PMID: 25130995 DERIVED

• 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.

  PMID: 23151431 DERIVED

• 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.

  PMID: 23127770 DERIVED

Related Links

• Click here for more information about this study on the TROG official website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide; Zoledronic Acid

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jim Denham, FRANZCR

  University of Newcastle, Australia

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 19, 2005
• Study Start: October 1, 2003
• Primary Completion: August 1, 2017
• Study Completion: August 1, 2017
• Last Updated: October 12, 2017

Record last verified: 2017-10

Locations

AU (18); NZ (6)