RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery

Prostate Cancer Clinical Trial

Official title:

Radiation Therapy and Androgen Deprivation Therapy in Treating Patients Who Have Undergone Surgery for Prostate Cancer (RADICALS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00541047
• Other study ID #: CDR0000571528
• Secondary ID: MRC-RADICALS-PR1
• Status: Completed
• Phase: Phase 3
• Start date: November 2007
• Est. completion date: July 27, 2022

Study information

• Verified date: November 2023
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4236
• Est. completion date: July 27, 2022
• Est. primary completion date: July 27, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 0 Years to 120 Years

Eligibility

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-a 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

Related Conditions & MeSH terms

• Gastrointestinal Complications
• Prostate Cancer
• Prostatic Neoplasms
• Sexual Dysfunction
• Urinary Complications

Intervention

Drug:
• bicalutamide

• goserelin acetate

• leuprolide acetate

Procedure:
• adjuvant therapy

• quality-of-life assessment

Radiation:
• radiation therapy

Locations

Country	Name	City	State
Canada	British Columbia Cancer Agency - Centre for the Southern Interior	Kelowna	British Columbia
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Ottawa Health Research Institute	Ottawa	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	William Harvey Hospital	Ashford	England
United Kingdom	Ayr Hospital	Ayr	Scotland
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Basingstoke and North Hampshire NHS Foundation Trust	Basingstoke	England
United Kingdom	Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust	Birmingham	England
United Kingdom	Glan Clwyd Hospital	Bodelwyddan	Wales
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Bradford Royal Infirmary	Bradford	England
United Kingdom	Bristol Haematology and Oncology Centre	Bristol	England
United Kingdom	Southmead Hospital	Bristol	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Walsgrave Hospital	Coventry	England
United Kingdom	Mid Cheshire Hospitals Trust- Leighton Hopsital	Crewe	England
United Kingdom	Mayday University Hospital	Croydon	England
United Kingdom	Doncaster Royal Infirmary	Doncaster	England
United Kingdom	Dorset County Hospital	Dorchester	England
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Princess Alexandra Hospital	Harlow	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	Leeds	England
United Kingdom	Lincoln County Hospital	Lincoln	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Helen Rollason Cancer Care Centre at North Middlesex Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Manchester	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Royal Gwent Hospital	Newport	Wales
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Queen's Hospital	Romford	England
United Kingdom	Rotherham General Hospital	Rotherham	England
United Kingdom	Hope Hospital	Salford	England
United Kingdom	Cancer Research Centre at Weston Park Hospital	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Stepping Hill Hospital	Stockport	England
United Kingdom	University Hospital of North Staffordshire	Stoke-On-Trent	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Hillingdon Hospital	Uxbridge	England
United Kingdom	Pinderfields General Hospital	Wakefield	Scotland
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England
United Kingdom	Cancer Care Centre at York Hospital	York	England

Sponsors (2)

Lead Sponsor	Collaborator
University College, London	Canadian Cancer Trials Group

Countries where clinical trial is conducted

Canada,  United Kingdom, 

References & Publications (3)

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 Resul — View 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 — View 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 rad — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-specific survival (i.e., death due to prostate cancer) (RADICALS-HD)		up 12 years
Primary	Freedom from distant metastases (any distance metastases or prostate cancer death) (RADICALS-RT)		up 12 years
Secondary	Freedom from treatment failure		up 12 years
Secondary	Clinical progression-free survival		up 12 years
Secondary	Overall survival		up 12 years
Secondary	Non-protocol hormone therapy		up 12 years
Secondary	Treatment toxicity		up 12 years
Secondary	Patient reported outcomes - EQ5D		up 12 years
Secondary	Freedom from biochemical progression (RADICALS-RT)		up 12 years