Clinical trial NCT01819285: Early Compared With Delayed Hormone Therapy in Treating Patients With Nonmetastatic Prostate Cancer
Official title: Phase III Comparison of Early vs Delayed Endocrine Manipulation (Orchiectomy or LHRH Agonist Therapy) in Previously Untreated Patients With Nonmetastatic Asymptomatic Carcinoma of the Prostate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Neoplasm, Prostate
Keywords: Malignant Neoplasm of Prostate
Tumor-node-metastasis (TNM) Staging Regional Lymph Nodes (N0-2)
Not suitable for local treatment with curative intent
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2013-03-27
Enrollment: 985
Sex: MALE
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Objectives

I. Compare, in a randomized Phase III multi-institutional setting, symptom-free survival time of patients with asymptomatic carcinoma of the prostate (T0-4, N0-2, M0) not suited for local curative treatment who are randomly assigned to immediate vs. delayed endocrine intervention (orchiectomy or luteinizing hormone releasing hormone (LHRH) agonist therapy).

II. Compare the overall survival of these two groups of patients.

III. Compare the time to first evidence of distant progression (N4 or M1) of these two treatment groups.

IV. Evaluate the prognostic significance of pretreatment laboratory data and monitor these parameters following endocrine therapy.

V. Study the prognosis of various sub-groups of patients stratified according to performance status, local tumor extent, nodal status, and choice of endocrine treatment.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically proven, newly diagnosed asymptomatic (with the exception of voiding disturbances) carcinoma of the prostate T0-4 N0-2 M0 which is not suitable for local treatment with curative intent (radical prostatectomy, radiation therapy).
* All T stages are acceptable (UICC 1982). The stage is determined by rectal palpation.
* Patients with regional lymph node metastases smaller than 5 cm (N0-2), determined either by CT or ultrasonography, preferable with cytologic confirmation.
* Life expectancy of at least six months.
* WHO performance status score 0-1.
* Informed consent. Patients must be prepared to undergo an orchiectomy or continuous treatment with a depot LHRH analogue.
* Continuous follow-up until death if possible.

Exclusion Criteria:

* Other malignancies diagnosed during the last 10 years, apart from treated basal cell carcinoma of the skin.
* Prostate cancer known for longer than one month before entering the study.
* Pain caused by the prostate cancer or its metastases.
* Any previous treatment for prostate cancer (radical prostatectomy, radiation therapy, endocrine treatment, etc.) Note: TUR-P for voiding disturbances is allowed at any time and is not an exclusion criterion.
* Patients with ureteric obstruction caused by local infiltration of prostatic cancer and other evidence of locally advanced disease which could cause fatal complications if untreated (e.g. rectal stenosis, thrombosis of pelvic veins).
* Patients with palpable or juxtaregional lymph node metastasis (paraaortic, supraclavicular, inguinal, N3-4).
* Patients with evidence of distant metastases (bone, lung, liver).
* Age over 80 years. Performance status WHO score 2, 3 and 4 (any reason).
* Patient who refuses orchiectomy or longterm subcutaneous implants of LHRH analogue in two monthly intervals.

Expected difficulties with follow-up for any reason.

Primary outcomes:
measure: Overall survival
timeFrame: 13 years from first patient in
Secondary outcomes:
measure: Overall symptom free survival time
timeFrame: 13 years from first patient in
measure: Time until first evidence of distant progression
timeFrame: 13 years from first patient in
measure: Prognostic importance of pretreatment laboratory data
timeFrame: 13 years from first patient in
measure: Prognosis of particular sub-groups
timeFrame: 13 years from first patient in
Other outcomes:
Locations:
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Urs Studer, MD
role: STUDY_CHAIR
References:
citation: Studer UE, Whelan P, Wimpissinger F, Casselman J, de Reijke TM, Knonagel H, Loidl W, Isorna S, Sundaram SK, Collette L; EORTC Genitourinary Cancer Group. Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up. Eur Urol. 2014 Nov;66(5):829-38. doi: 10.1016/j.eururo.2013.07.024. Epub 2013 Jul 24.