RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery

University College London (UCL)

Status and phase: Completed; Phase 3

Conditions: Sexual Dysfunction; Prostate Cancer; Urinary Complications; Gastrointestinal Complications

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

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00541047

MRC-RADICALS-PR10

2006-000205-34 (EudraCT Number)

CDR0000571528

ISRCTN40814031

PR13

00316/0223/001-0001 (Other Identifier)

NCT00541047 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4,236 patients

Sex: Male

Ages: Under 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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4,236 participants in 5 patient groups

RADICALS-RT: Early RT

Experimental group

Treatment:

Procedure: adjuvant therapy

Procedure: quality-of-life assessment

Radiation: radiation therapy

RADICALS-RT: Salvage RT

Experimental group

Treatment:

Procedure: adjuvant therapy

Procedure: quality-of-life assessment

Radiation: radiation therapy

RADICALS-HD: Radiotherapy Alone

Experimental group

Treatment:

Procedure: adjuvant therapy

Radiation: radiation therapy

RADICALS-HD: Radiotherapy + 6 months

Experimental group

Treatment:

Drug: leuprolide acetate

Procedure: adjuvant therapy

Drug: goserelin acetate

Radiation: radiation therapy

Drug: bicalutamide

RADICALS-HD: Radiotherapy + 24 months

Experimental group

Treatment:

Drug: leuprolide acetate

Procedure: adjuvant therapy

Drug: goserelin acetate

Radiation: radiation therapy

Drug: bicalutamide