Clinical trial NCT00541047: RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery
Official title: Radiation Therapy and Androgen Deprivation Therapy in Treating Patients Who Have Undergone Surgery for Prostate Cancer (RADICALS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastrointestinal Complications
Prostate Cancer
Sexual Dysfunction
Urinary Complications
Keywords: sexual dysfunction
urinary complications
gastrointestinal complications
adenocarcinoma of the prostate
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: Canadian Cancer Trials Group
First posted: 2007-10-08
Enrollment: 4236
Sex: MALE
Minimum age (years): 0
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy, such as goserelin, leuprolide, or bicalutamide, may lessen the amount of androgens made by the body. Giving radiation therapy together with androgen deprivation therapy may kill more prostate cancer cells.

PURPOSE: This randomized phase III trial is studying how well giving radiation therapy together with androgen deprivation therapy works in treating patients who have undergone surgery for prostate cancer.

Detailed description: OBJECTIVES:

* Assess the timing of radiotherapy and the use of hormone therapy in conjunction with post-operative radiotherapy.
* Determine the impact of radiotherapy on general quality of life, sexual function, urinary function, and bowel function.
* Determine the impact of duration of hormone therapy on general quality of life and sexual function.

OUTLINE: This is a multicenter study. Patients requiring immediate radiotherapy (RT) are assigned to arm I; patients do not require immediate RT are assigned to arm II. Patients for whom the need of immediate post-operative radiotherapy are uncertain undergo radiotherapy timing randomization within 3 months after surgery and are randomized to 1 of 2 radiotherapy arms.

* Arm I (immediate RT): Within 2 months after randomization, patients undergo radiotherapy to the prostate bed once a day, 5 days a week, for 4 (20 fractions total) or 6.5 weeks (33 fractions total). They may also undergo radiotherapy to the pelvic lymph nodes once a day, 5 days a week, for 4.5 weeks (23 fractions total) at the investigator's discretion.
* Arm II (early salvage RT in case of PSA failure): Within 2 months of confirmation of post-operative biochemical failure, patients undergo radiotherapy as in arm I.

Patients undergoing immediate RT and patients who eventually need early salvage RT undergo hormone therapy duration randomization before the administration of post-operative radiotherapy. Patients are randomized to 1 of 3 hormone therapy arms.

* Arm III (no hormone therapy): Patients do not receive hormone therapy. They receive post-operative RT alone as described above in arm I or II.
* Arm IV (RT and short-term hormone therapy): Beginning approximately 2 months prior to the start of RT, patients receive hormone therapy for 6 months. Hormone therapy\* may comprise of LHRH agonist (gonadotrophin-releasing hormone analogue \[GnRHa\] \[e.g., goserelin or leuprolide acetate\]) or bicalutamide daily.
* Arm V (RT and long-term hormone therapy): Beginning approximately 2 months prior to the start of RT, patients receive hormone therapy for 24 months. Hormone therapy\* may comprise of LHRH agonist (gonadotrophin-releasing hormone analogue \[GnRHa\] \[e.g., goserelin or leuprolide acetate\]) or bicalutamide daily.

NOTE: \*For Canadian patients, hormonal therapy will consist of LHRH analog (leuprolide acetate) therapy only.

Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed using self-administered questionnaires at baseline and 1, 5, and 10 years after randomization. Health economics information is also collected via patient-administered questionnaires (EQ-5D) at baseline and at 1, 5 and 10 years after randomization.

After completion of study treatment, patients are followed for 7 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

Inclusion criteria:

* Diagnosis of nonmetastatic adenocarcinoma of the prostate
* Must have undergone radical prostatectomy
* Post-operative serum prostate-specific antigen (PSA) \< 0.4 ng/mL
* No post-operative biochemical failure, defined as EITHER two consecutive rises in PSA and final PSA \> 0.1 ng/mL OR three consecutive rises in PSA (for patients undergoing hormone therapy duration randomization)

Exclusion criteria:

* Known distant metastases from prostate cancer
* PSA \> 5 ng/mL at the time of hormone randomization (for patients undergoing hormone therapy duration randomization)

PATIENT CHARACTERISTICS:

* No other active malignancy likely to interfere with protocol treatment or follow-up

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

* See Disease Characteristics
* Co-enrollment to other trials is permitted, providing this does not interfere with the outcome measures
* 5-α reductase inhibitors, soya, selenium, and vitamin E are acceptable non-trial therapies

Exclusion criteria:

* Prior hormone therapy
* Bilateral orchidectomy
* Prior pelvic radiotherapy
* Neoadjuvant treatment
* Other concurrent therapies for prostate cancer (e.g., estrogens or cytotoxic chemotherapy) prior to disease progression

Primary outcomes:
measure: Disease-specific survival (i.e., death due to prostate cancer) (RADICALS-HD)
timeFrame: up 12 years
measure: Freedom from distant metastases (any distance metastases or prostate cancer death) (RADICALS-RT)
timeFrame: up 12 years
Secondary outcomes:
measure: Freedom from treatment failure
timeFrame: up 12 years
measure: Clinical progression-free survival
timeFrame: up 12 years
measure: Overall survival
timeFrame: up 12 years
measure: Non-protocol hormone therapy
timeFrame: up 12 years
measure: Treatment toxicity
timeFrame: up 12 years
measure: Patient reported outcomes - EQ5D
timeFrame: up 12 years
measure: Freedom from biochemical progression (RADICALS-RT)
timeFrame: up 12 years
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Cancer Centre
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Ashford
country: United Kingdom
facility: William Harvey Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: England
city: Bristol
country: United Kingdom
facility: Southmead Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Crewe
country: United Kingdom
facility: Mid Cheshire Hospitals Trust- Leighton Hopsital
state: England
city: Croydon
country: United Kingdom
facility: Mayday University Hospital
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Harlow
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Lincoln
country: United Kingdom
facility: Lincoln County Hospital
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Royal Marsden - London
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Romford
country: United Kingdom
facility: Queen's Hospital
state: England
city: Rotherham
country: United Kingdom
facility: Rotherham General Hospital
state: England
city: Salford
country: United Kingdom
facility: Hope Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Stockport
country: United Kingdom
facility: Stepping Hill Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Uxbridge
country: United Kingdom
facility: Hillingdon Hospital
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Ayr
country: United Kingdom
facility: Ayr Hospital
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Wakefield
country: United Kingdom
facility: Pinderfields General Hospital
state: Scotland
city: Bodelwyddan
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: Wales
city: Newport
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Christopher Parker, MD
role: STUDY_CHAIR
References:
citation: Parker CC, Clarke NW, Catton C, Kynaston H, Cook A, Cross W, Davidson C, Goldstein C, Logue J, Maniatis C, Petersen PM, Neville P, Payne H, Persad R, Pugh C, Stirling A, Saad F, Parulekar WR, Parmar MKB, Sydes MR. RADICALS-HD: Reflections before the Results are Known. Clin Oncol (R Coll Radiol). 2022 Sep;34(9):593-597. doi: 10.1016/j.clon.2022.06.004. Epub 2022 Jul 6. No abstract available.
citation: Parker CC, Clarke NW, Cook AD, Kynaston HG, Petersen PM, Catton C, Cross W, Logue J, Parulekar W, Payne H, Persad R, Pickering H, Saad F, Anderson J, Bahl A, Bottomley D, Brasso K, Chahal R, Cooke PW, Eddy B, Gibbs S, Goh C, Gujral S, Heath C, Henderson A, Jaganathan R, Jakobsen H, James ND, Kanaga Sundaram S, Lees K, Lester J, Lindberg H, Money-Kyrle J, Morris S, O'Sullivan J, Ostler P, Owen L, Patel P, Pope A, Popert R, Raman R, Roder MA, Sayers I, Simms M, Wilson J, Zarkar A, Parmar MKB, Sydes MR. Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial. Lancet. 2020 Oct 31;396(10260):1413-1421. doi: 10.1016/S0140-6736(20)31553-1. Epub 2020 Sep 28.
citation: Vale CL, Fisher D, Kneebone A, Parker C, Pearse M, Richaud P, Sargos P, Sydes MR, Brawley C, Brihoum M, Brown C, Chabaud S, Cook A, Forcat S, Fraser-Browne C, Latorzeff I, Parmar MKB, Tierney JF; ARTISTIC Meta-analysis Group. Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data. Lancet. 2020 Oct 31;396(10260):1422-1431. doi: 10.1016/S0140-6736(20)31952-8. Epub 2020 Sep 28.