RADAR Trial – Randomised Androgen Deprivation and Radiotherapy

Purpose
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.

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.

Conditions

Study Type

Interventional

Study Design

Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy StudyAfter informed consent is given and eligibility is checked patients will be randomised to one of four trial arms:- 6 months of androgen blockade with an LH-RH analogue (5 months before start of radiotherapy) (STAD), – 18 months of androgen blockade with an LH-RH analogue (starting 5 months before start of radiotherapy) (ITAD), – 18 months of therapy with zoledronic acid 4 mg by intravenous infusion every 3 months for 18 months beginning concurrently with STAD – 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 centreRadiation 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.

Further Details

Primary Outcomes: Biochemical Failure; SurvivalSecondary Outcomes: Patterns of failure; Treatment related toxicity; Quality of life; Bone density changes; Influence of histopathology; Influence of radiation dose

Study Start

Oct 2004; Expected completion: Oct 2021; Last follow-up: Oct 2020; Data entry closure: Oct 2021

Eligibility & Criteria

Ages Eligible for Study: 18 Years and aboveGenders Eligible for Study: Male CriteriaInclusion Criteria:1. Histological confirmation of adenocarcinoma of the prostate in the three months prior to randomisation 2. 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. 3. Primary tumour stage T2b – 4 (UICC 2002), or T2a providing biopsies demonstrate Gleason score 7 or more, and presenting PSA 10 or more 4. PSA value obtained within one month of randomisation 5. 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 6. ECOG performance status 0 – 1 7. No concurrent medical conditions likely to significantly reduce prospects of 5 year survival 8. Patient accessible to follow up at intervals specified in protocol 9. Written informed consent given (signed by both patient and investigator prior to randomisation) Exclusion Criteria:1. Previous or concurrent malignancy within previous 5 years except for non-melanomatous skin cancer 2. Prostatectomy 3. Prior pelvic radiotherapy 4. Prior hormone treatment for prostate cancer 5. Inability to complete self administered QOL questionnaire 6. Prior bisphosphonate therapy 7. Serum creatinine > 2 x ULN 8. Osteoporosis resulting in >30% loss in vertebral height in one or more thoraco-lumbar vertebrae 9. Liver disease resulting in ALT or AST levels >3 x ULN 10. Prolonged continuous glucocorticoid therapy > 10 mg/day of prednisone equivalent (>6 months) 11. Current treatment with bisphosphonate

Total Enrolment

1000

Contact Details

Australia, New South WalesNewcastle Mater Misericordiae Hopsital, Newcastle, New South Wales, 2298, Australia; Recruiting Kristen Palmer, BS +61 (0) 2 49211 892 Kristen.palmer@mater.health.nsw.gov.au Michelle Hall +61 (0) 2 49211 462 Michelle.hall@mater.health.nsw.gov.au Jim Denham, FRANZCR, Principal Investigator