RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery

• ClinicalTrials.gov Identifier: NCT00541047
• Recruitment Status: Completed
• First Posted: October 8, 2007
• Last Update Posted: November 13, 2023
• Sponsor: University College, London
• Collaborator: Canadian Cancer Trials Group
• Information provided by (Responsible Party): Cheryl Pugh, University College, London

Tracking Information

• First Submitted Date: October 5, 2007
• First Posted Date: October 8, 2007
• Last Update Posted Date: November 13, 2023
• Study Start Date: November 2007
• Actual Primary Completion Date: July 27, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 8, 2023)

• Disease-specific survival (i.e., death due to prostate cancer) (RADICALS-HD) [ Time Frame: up 12 years ]
• Freedom from distant metastases (any distance metastases or prostate cancer death) (RADICALS-RT) [ Time Frame: up 12 years ]

• Original Primary Outcome Measures (submitted: October 5, 2007): Disease-specific survival (i.e. death due to prostate cancer)

Current Secondary Outcome Measures (submitted: November 8, 2023)

• Freedom from treatment failure [ Time Frame: up 12 years ]
• Clinical progression-free survival [ Time Frame: up 12 years ]
• Overall survival [ Time Frame: up 12 years ]
• Non-protocol hormone therapy [ Time Frame: up 12 years ]
• Treatment toxicity [ Time Frame: up 12 years ]
• Patient reported outcomes - EQ5D [ Time Frame: up 12 years ]
• Freedom from biochemical progression (RADICALS-RT) [ Time Frame: up 12 years ]

Original Secondary Outcome Measures (submitted: October 5, 2007)

• Freedom from treatment failure
• Clinical progression-free survival
• Overall survival
• Non-protocol hormone therapy
• Treatment toxicity
• Patient reported outcomes

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)

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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: bicalutamide
• Drug: goserelin acetate
• Drug: leuprolide acetate
• Procedure: adjuvant therapy
• Procedure: quality-of-life assessment
• Radiation: radiation therapy

Study Arms

• Experimental: RADICALS-RT: Early RT
  Interventions:

  • Procedure: adjuvant therapy
  • Procedure: quality-of-life assessment
  • Radiation: radiation therapy
• Experimental: RADICALS-RT: Salvage RT
  Interventions:

  • Procedure: adjuvant therapy
  • Procedure: quality-of-life assessment
  • Radiation: radiation therapy
• Experimental: RADICALS-HD: Radiotherapy Alone
  Interventions:

  • Procedure: adjuvant therapy
  • Radiation: radiation therapy
• Experimental: RADICALS-HD: Radiotherapy + 6 months
  Interventions:

  • Drug: bicalutamide
  • Drug: goserelin acetate
  • Drug: leuprolide acetate
  • Procedure: adjuvant therapy
  • Radiation: radiation therapy
• Experimental: RADICALS-HD: Radiotherapy + 24 months
  Interventions:

  • Drug: bicalutamide
  • Drug: goserelin acetate
  • Drug: leuprolide acetate
  • Procedure: adjuvant therapy
  • Radiation: radiation therapy

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 12, 2017): 4236
• Original Enrollment (submitted: October 5, 2007): 6100
• Actual Study Completion Date: July 27, 2022
• Actual Primary Completion Date: July 27, 2022 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 0 Years to 120 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United Kingdom

Administrative Information

• NCT Number: NCT00541047
• Other Study ID Numbers: CDR0000571528; MRC-RADICALS-PR10 ( Other Identifier: MRC at UCL ); ISRCTN40814031 ( Registry Identifier: ISRCTN ); 2006-000205-34 ( EudraCT Number ); 00316/0223/001-0001 ( Other Identifier: CTA ); PR13 ( Other Grant/Funding Number: Canadian Cancer Society - Research Institute )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: Data can be shared on request via emailing mrcctu.radical@ucl.ac.uk

• Current Responsible Party: Cheryl Pugh, University College, London
• Original Responsible Party: Not Provided
• Current Study Sponsor: University College, London
• Original Study Sponsor: Medical Research Council
• Collaborators: Canadian Cancer Trials Group

Investigators

• Study Chair: Christopher Parker, MD; Royal Marsden NHS Foundation Trust

• PRS Account: University College, London
• Verification Date: November 2023