Clinical trial NCT00110162: Androgen Deprivation Therapy in Treating Patients With Prostate Cancer
Official title: A Collaborative Randomized Phase III Trial: The Timing of Intervention With Androgen Deprivation in Prostate Cancer Patients With Rising PSA
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer
stage III prostate cancer
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-05-04
Enrollment: 2000
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

OUTLINE: This 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.

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

Eligibility criteria: DISEASE 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

Primary outcomes:
measure: Death from any cause at 8 years
Secondary outcomes:
measure: Cancer specific survival
measure: Clinical progression
measure: Time to first androgen independence
measure: Complication rate incidence and timing (e.g., cord compression, pathological fracture)
measure: Treatment-related morbidity (including cognitive, osteoporosis)
measure: Prognostic factors for progression (delayed group)
measure: EORTC Quality of life - general QLQC30 and prostate module for Quality of life annually for 5 years
measure: CTC v3.0 Survival endpoints: actuarial analysis at eight years
measure: Morbidity continuously
Other outcomes:
Locations:
city: Campbelltown
country: Australia
facility: Cancer Therapy Centre at Campbelltown Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Cancer Care Centre at Nepean Hospital
state: New South Wales
city: Liverpool
country: Australia
facility: Cancer Therapy Centre at Liverpool Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Cancer Centre at Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Institute for Cancer Research at Westmead Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Tugun
country: Australia
facility: East Coast Cancer Centre
state: Queensland
city: Ashford
country: Australia
facility: Urological Solutions
state: South Australia
city: Daws Park
country: Australia
facility: Repatriation General Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Geelong
country: Australia
facility: Geelong Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
city: Warragul
country: Australia
facility: West Gippsland Hospital
state: Victoria
city: Christchurch
country: Australia
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
Study officials:
affiliation: Peter MacCallum Cancer Centre, Australia
name: Gillian M. Duchesne, MD, FRCR
role: STUDY_CHAIR
References:
citation: Duchesne GM, Woo HH, King M, Bowe SJ, Stockler MR, Ames A, D'Este C, Frydenberg M, Loblaw A, Malone S, Millar J, Tai KH, Turner S. Health-related quality of life for immediate versus delayed androgen-deprivation therapy in patients with asymptomatic, non-curable prostate cancer (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1192-1201. doi: 10.1016/S1470-2045(17)30426-6. Epub 2017 Jul 28.
citation: Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, King M, Ledwich L, Loblaw A, Malone S, Millar J, Milne R, Smith RG, Spry N, Stockler M, Syme RA, Tai KH, Turner S. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016 Jun;17(6):727-737. doi: 10.1016/S1470-2045(16)00107-8. Epub 2016 May 4.