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

Condition(s) targeted: Gastrointestinal Complications; Prostate Cancer; Sexual Dysfunction; Urinary Complications

Intervention: bicalutamide (Drug); goserelin acetate (Drug); leuprolide acetate (Drug); adjuvant therapy (Procedure); quality-of-life assessment (Procedure); radiation therapy (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: Medical Research Council

Official(s) and/or principal investigator(s):
Christopher Parker, MD, Study Chair, Affiliation: Royal Marsden NHS Foundation Trust

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.

Official title: RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery

Study design: Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Disease-specific survival (i.e., death due to prostate cancer)

Secondary outcome:

Freedom from treatment failure

Clinical progression-free survival

Overall survival

Non-protocol hormone therapy

Treatment toxicity

Patient reported outcomes

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.

Minimum age: N/A. Maximum age: N/A. Gender(s): Male.

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

British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna, British Columbia V1Y 5L3, Canada; Recruiting
Contact Person, Phone: 250-712-3900

British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver, British Columbia V5Z 4E6, Canada; Recruiting
Contact Person, Phone: 604-877-6000

William Harvey Hospital, Ashford-Kent, England TN24 0LZ, United Kingdom; Recruiting
Contact Person, Phone: 44-1227-766-877

North Devon District Hospital, Barnstaple, England EX31 4JB, United Kingdom; Recruiting
Contact Person, Phone: 44-1392-402-114

Basingstoke and North Hampshire NHS Foundation Trust, Basingstoke, England RG24 9NA, United Kingdom; Recruiting
Contact Person, Phone: 44-1483-406-823

Queen Elizabeth Hospital at University Hospital of Birmingham NHS Trust, Birmingham, England B15 2TH, United Kingdom; Recruiting
Contact Person, Phone: 44-121-472-1311

Royal Bournemouth Hospital, Bournemouth, England BH7 7DW, United Kingdom; Recruiting
Contact Person, Phone: 44-1202-448-435

Bradford Royal Infirmary, Bradford, England BD9 6RJ, United Kingdom; Recruiting
Contact Person, Phone: 44-113-206-7630

Southmead Hospital, Bristol, England BS10 5NB, United Kingdom; Recruiting
Contact Person, Phone: 44-117-959-5147

Bristol Haematology and Oncology Centre, Bristol, England BS2 8ED, United Kingdom; Recruiting
Amit Bahl, MD, Phone: 44-117-928-2468, Email: amit.bahl@ubht.nhs.uk

Addenbrooke's Hospital, Cambridge, England CB2 2QQ, United Kingdom; Recruiting
Helen Patterson, MD, Phone: 44-122324-5151 ext. 2523 and 2

Kent and Canterbury Hospital, Canterbury, England CT1 3NG, United Kingdom; Recruiting
Contact Person, Phone: 44-1227-766-877

Walsgrave Hospital, Coventry, England CV2 2DX, United Kingdom; Recruiting
Contact Person, Phone: 44-24-7696-7488

Mid Cheshire Hospitals Trust- Leighton Hopsital, Crewe, England CW1 4QJ, United Kingdom; Recruiting
J. P. Logue, MD, Phone: 44-1270-255-141

Mayday University Hospital, Croydon, England, United Kingdom; Recruiting
Contact Person, Phone: 44-20-8725-3305

Doncaster Royal Infirmary, Doncaster, England DN2 5LT, United Kingdom; Recruiting
Contact Person, Phone: 44-114-226-5000

Dorset County Hospital, Dorchester, England DT1 2JY, United Kingdom; Recruiting
Adrian Crellin, FRCP, FRCR, Phone: 44-1305-251-150

Princess Alexandra Hospital, Essex, England CM20 1QX, United Kingdom; Recruiting
Contact Person, Phone: 44-20-887-2687

Royal Devon and Exeter Hospital, Exeter, England EX2 5DW, United Kingdom; Recruiting
Contact Person, Phone: 44-1392-402-105

St. Luke's Cancer Centre at Royal Surrey County Hospital, Guildford, England GU2 7XX, United Kingdom; Recruiting
Contact Person, Phone: 44-1483-406-823

Ipswich Hospital, Ipswich, England IP4 5PD, United Kingdom; Recruiting
Contact Person, Phone: 44-1473-704-389

Leeds Cancer Centre at St. James's University Hospital, Leeds, England LS9 7TF, United Kingdom; Recruiting
Contact Person, Phone: 44-113-206-7822

Lincoln County Hospital, Lincoln, England LN2 5QY, United Kingdom; Recruiting
Contact Person, Phone: 44-1522-572-215

University College Hospital, London, England NW1 2BU, United Kingdom; Recruiting
Contact Person, Phone: 44-20-7380-9105

Royal Marsden - London, London, England SW3 6JJ, United Kingdom; Recruiting
Contact Person, Phone: 44-20-7808-2788

Helen Rollason Cancer Care Centre at North Middlesex Hospital, London, England N18 1QX, United Kingdom; Recruiting
Contact Person, Phone: 44-20-887-2687

Guy's Hospital, London, England SE1 9RT, United Kingdom; Recruiting
Contact Person, Phone: 44-20-7188-4219

Maidstone Hospital, Maidstone, England ME16 9QQ, United Kingdom; Recruiting
Sharon Beesley, Phone: 44-1622-729-000

Christie Hospital, Manchester, England M20 4BX, United Kingdom; Recruiting
John Logue, Phone: 44-161-446-3407, Email: john.logue@christie-tr.nwest.nhs.uk

Clatterbridge Centre for Oncology, Merseyside, England CH63 4JY, United Kingdom; Recruiting
Contact Person, Phone: 44-151-334-1155

James Cook University Hospital, Middlesbrough, England TS4 3BW, United Kingdom; Recruiting
Contact Person, Phone: 44-1642-850-830

Mount Vernon Cancer Centre at Mount Vernon Hospital, Northwood, England HA6 2RN, United Kingdom; Recruiting
Peter Ostler, MD, Phone: 44-1923-844-592

Derriford Hospital, Plymouth, England PL6 8DH, United Kingdom; Recruiting
Contact Person, Phone: 44-1752-517-809

Dorset Cancer Centre, Poole Dorset, England BH15 2JB, United Kingdom; Recruiting
Contact Person, Phone: 44-1202-448-263

Queen's Hospital, Romford, England RM7 0AG, United Kingdom; Recruiting
Contact Person, Phone: 44-1708-435-428

Rotherham General Hospital, Rotherham, England S60 2UD, United Kingdom; Recruiting
Contact Person, Phone: 44-114-226-5000

Hope Hospital, Salford, England M6 8HD, United Kingdom; Recruiting
Noel Clarke, Phone: 44-161-206-5568

Cancer Research Centre at Weston Park Hospital, Sheffield, England S1O 2SJ, United Kingdom; Recruiting
Contact Person, Phone: 44-114-226-5000

Southampton General Hospital, Southampton, England SO16 6YD, United Kingdom; Recruiting
Catherine Heath, Phone: 44-23-8079-4202

Stepping Hill Hospital, Stockport, England SK2 7JE, United Kingdom; Recruiting
John Logue, Phone: 44-161-419-5883

University Hospital of North Staffordshire, Stoke-On-Trent, England ST4 7LN, United Kingdom; Recruiting
Contact Person, Phone: 44-1782-554-301

Royal Marsden - Surrey, Sutton, England SM2 5PT, United Kingdom; Recruiting
Christopher Parker, MD, Phone: 44-208-661-3425

Torbay Hospital, Torquay, England TQ2 7AA, United Kingdom; Recruiting
Anna Lydon, MD, Phone: 44-1803-655-376

Hillingdon Hospital, Uxbridge, England UB8 3NN, United Kingdom; Recruiting
Alvan J. Pope, Phone: 44-1895-238-282

Southend University Hospital NHS Foundation Trust, Westcliff-On-Sea, England SS0 0RY, United Kingdom; Recruiting
Contact Person, Phone: 44-1702-435-555

Cancer Care Centre at York Hospital, York, England Y031 8HE, United Kingdom; Recruiting
M. Stower, Phone: 44-1904-725-972

London Regional Cancer Program at London Health Sciences Centre, London, Ontario N6A 4L6, Canada; Recruiting
Contact Person, Phone: 519-685-8615

Ottawa Health Research Institute, Ottawa, Ontario K1Y 4E9, Canada; Recruiting
Contact Person, Phone: 613-761-4395

Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
Contact Person, Phone: 416-946-2811

Aberdeen Royal Infirmary, Aberdeen, Scotland AB25 2ZN, United Kingdom; Recruiting
Contact Person, Phone: 44-1224-551-273

Ayr Hospital, Ayr, Scotland KA6 6DX, United Kingdom; Recruiting
Contact Person, Phone: 44-141-301-7062

Edinburgh Cancer Centre at Western General Hospital, Edinburgh, Scotland EH4 2XU, United Kingdom; Recruiting
Contact Person, Phone: 44-131-537-3036

Beatson West of Scotland Cancer Centre, Glasgow, Scotland G12 0YN, United Kingdom; Recruiting
Contact Person, Phone: 44-141-301-7062

Pinderfields General Hospital, Wakefield, Scotland WF1 4DG, United Kingdom; Recruiting
Contact Person, Phone: 44-113-206-7822

University Hospital of Wales, Cardiff, Wales CF14 4XW, United Kingdom; Recruiting
Howard Kynaston, Phone: 44-2920-745-094

Velindre Cancer Center at Velindre Hospital, Cardiff, Wales CF14 2TL, United Kingdom; Recruiting
John Staffurth, MD, Phone: 44-292-061-5888 ext. 6353

Royal Gwent Hospital, Newport Gwent, Wales NP9 2UB, United Kingdom; Recruiting
Contact Person, Phone: 44-1633-234-975

Glan Clwyd Hospital, Rhyl, Denbighshire, Wales LL 18 5UJ, United Kingdom; Recruiting
Contact Person, Phone: 44-1745-445-158

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: October 2007
Last updated: February 19, 2012