Androgen Deprivation Therapy in Treating Patients With Prostate Cancer

Rationale: Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy may stop the adrenal glands from making androgens.

Purpose: This randomized phase III trial is studying how well androgen deprivation therapy works in treating patients with prostate cancer.

Official Title

Phase III Randomized Study of Delayed Versus Immediate Androgen Deprivation Therapy in Patients With Prostate Cancer

Conditions

Study Type

Interventional

Study Design

TreatmentThis is a multicenter, randomized, controlled study. Patients in group 1 are stratified according to prior therapy (prostatectomy vs radiotherapy vs prostatectomy and radiotherapy), relapse-free interval (< 2 years vs ≥ 2 years), type of planned androgen deprivation therapy (ADT) (continuous vs intermittent), and participating center. Patients in group 2 are stratified according to type of planned ADT (continuous vs intermittent), disease type (localized vs metastatic), and participating center. Patients in both groups are randomized to 1 of 2 treatment arms. Arm I (delayed ADT): Beginning at least 2 years after study entry or after exhibiting evidence of significant disease progression*, patients receive either continuous ADT OR intermittent ADT comprising either bilateral orchiectomy OR luteinizing hormone-releasing hormone agonist with or without oral antiandrogen therapy. Arm II (immediate ADT): Beginning immediately after randomization, patients receive either continuous ADT OR intermittent ADT as in arm I. NOTE: *Patients in group 1 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: prostate-specific antigen (PSA) doubling time of < 12 months with PSA ≥ 10 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart OR development of metastases or symptoms. Patients in group 2 begin delayed ADT at least 2 years after study entry unless 1 of the following clinical criteria is present: development of symptoms OR PSA ≥ 60 ng/mL OR PSA doubling time of ≤ 6 months based on 3 consecutive measurements obtained ≥ 2 months apart. After 9 months of ADT, all patients are assessed for response. Patients with PSA < 4 ng/mL may discontinue ADT. These patients are followed every 3 months. Treatment may be restarted when PSA is > 20 ng/mL OR PSA is > the PSA level at study entry OR at clinical progression. Quality of life is assessed at baseline, every 6 months for 2 years, and then annually for 3 years.Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then periodically thereafter at the discretion of the principal investigator.

Further Details

OBJECTIVES:Primary- Compare overall survival (with acceptable morbidity) of patients with prostate cancer treated with delayed vs immediate androgen deprivation therapy (ADT). Secondary- Compare cancer-specific survival of patients treated with these regimens. – Compare clinical progression in patients treated with these regimens. – Compare time to first androgen independence in patients treated with these regimens. – Compare complication rate incidence and timing (e.g., cord compression or pathological failure) in patients treated with these regimens. – Compare treatment-related morbidity (including cognitive morbidity or osteoporosis) in patients treated with these regimens. – Compare quality of life of patients treated with these regimens. – Determine prognostic factors for progression in patients treated with delayed ADT.

Study Start

Eligibility & Criteria

Genders Eligible for Study: Both CriteriaDisease characteristics:- Histologically confirmed adenocarcinoma of the prostate – Prostate-specific antigen (PSA) relapse OR incurable disease diagnosed within the past 2 months AND meets criteria for either of the following groups: Group 1 In PSA relapse after definitive radical treatment (prostatectomy or radiotherapy), as evidenced by 1 the following: Post-prostatectomy PSA level ≥ 0.2 ng/mL At least 3 rising PSA levels (post-radiotherapy) obtained ≥ 1 month apart, with the last PSA obtained within the past 2 months No metastatic disease by bone scan or abdomino-pelvic CT scan Group 2 Not suitable for radical treatment at primary diagnosis Not planning to receive curative treatment Localized or metastatic disease No symptomatic disease requiring radiotherapy or immediate hormonal therapy No symptomatic disease requiring therapy Patient characteristics:Age- Any age Performance status- Not specified Life expectancy- At least 5 years Hematopoietic- Not specified Hepatic- Not specified Renal- Not specified Other- No other significant comorbid condition that would limit life expectancy to < 5 years Prior concurrent therapy:Biologic therapy- Not specified Chemotherapy- Not specified Endocrine therapy- At least 12 months since prior androgen deprivation therapy (ADT) administered in the neoadjuvant or concurrent (with radiotherapy) setting (group 1) No prior ADT (group 2) Radiotherapy- See Disease Characteristics, See Endocrine therapy Surgery- See Disease Characteristics Other- No concurrent enrollment in TROG-96.01 or TROG-RADAR protocols

Total Enrolment

A total of 300-2,000 patients will be accrued for this study within 2-5 years.

Contact Details

Australia, New South WalesCancer Therapy Centre at Liverpool Hospital, Liverpool, New South Wales, 2170, Australia; Recruiting Andrew Kneebone 6-12-9828-5282 andrew.kneebone@swsahs.gov.au Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia; Recruiting George Hruby, MD 61-2-9767-5112 Sydney Cancer Centre at Royal Prince Alfred Hospital, Sydney, New South Wales, 2050, Australia; Recruiting George Hruby, MD 61-2-9515-8057 ghruby@email.cs.nsw.gov.au Westmead Hospital, Westmead, New South Wales, 2145, Australia; Recruiting Sandra Turner 61-2-9845-6499 Australia, QueenslandEast Coast Cancer Centre, Tugun, Queensland, 4224, Australia; Recruiting David Christie, MD 61-7-5598-0366 Mater Medical Centre, South Brisbane, Queensland, 4101, Australia; Recruiting Guy Bryant 6-17-3840-3255 guy-bryant@health.qld.gov.au Princess Alexandra Hospital, Brisbane, Queensland, 4102, Australia; Recruiting Margot Lehman 61-7-3240-6799 Royal Brisbane and Women’s Hospital, Brisbane, Queensland, 4029, Australia; Recruiting Lizbeth Kenny 61-7-3636-8111 Australia, South AustraliaRepatriation General Hospital, Daws Park, South Australia, 5041, Australia; Recruiting Alan Stapleton 61-8-8275-1927 alan.stapleton@rgh.sa.gov.au Urological Solutions, Ashford, South Australia, 5035, Australia; Recruiting Graham Sinclair, MD 61-8-8297-3877 Australia, VictoriaAlfred Hospital, Melbourne, Victoria, 3004, Australia; Recruiting Jeremy Millar 61-3-9276-2337 jeremy.millar@med.monash.edu.au Geelong Hospital, Geelong, Victoria, 3200, Australia; Recruiting Michael Francis, MBBS, FRACR 6-13-5226-7644 Peter MacCallum Cancer Centre, Melbourne, Victoria, 3002, Australia; Recruiting Gillian M. Duchesne, MD, FRCR 61-3-9656-1004 gillian.duchesne@petermac.org West Gippsland Hospital, Warragul, Victoria, 3820, Australia; Recruiting William Straffon, MD 61-3-5623-0857