Clinical trial NCT01366053: Hormone Sensitive Prostate Cancer Patients Switched to Degarelix Therapy After Failing on GnRH Agonists
Official title: Hormone Sensitive Prostate Cancer Patients Switched to Degarelix Therapy After Failing on GnRH Agonists: A Prospective, Observational, Phase IV Study (DELAY)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Prostate Cancer
Keywords: Prostate Cancer
Androgen Deprivation Therapy
Agonist
Antagonist
PSA Failure
PSA Rise
Lead sponsor: CMX Research
Sponsor class: OTHER
Collaborators: name: Ferring Pharmaceuticals
First posted: 2011-06-03
Enrollment: 125
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with prostate cancer failing androgen deprivation therapy can be investigated in this trial.

Brief summary: This Phase IV observational trial is intended to identify patients who are failing GnRH agonist therapy as evidenced by a rising PSA and who have yet to initiate secondary manoeuvres involving antiandrogens. This group may include both non-metastatic as well as metastatic patients. The trial will determine if these patients will benefit from switching to Degarelix. It will assess the effect of Degarelix's direct mode of action on androgen levels and whether continuous use of Degarelix improves disease progression.

As per the CUA Guidelines for the Management of CRPC, because the androgen receptor remains active in most patients who have developed castration resistant disease, it is recommended that ADT should be continued (LEVEL 3, GRADE C). Therefore, it is logical to continue patients on Degarelix throughout the castrate resistant period. This will allow for the gathering of data that is currently unknown within this setting, such as the effect of combined treatment with antiandrogens as well as chemotherapy and other castrate resistant treatments.

Detailed description: This trial will include hormone sensitive prostate cancer patients switched to Degarelix therapy after failing on GnRH agonists but prior to use of secondary hormonal treatments such as antiandrogens. The purpose of this trial is to determine the effect of Degarelix's direct mode of action on androgen levels and whether continuous use of Degarelix improves disease progression.

This is an open-label, multi-centre, Phase IV observational trial with s.c. injections of Degarelix one-month depot in patients with advanced prostate cancer.

The visit frequency is once a month (28-day intervals), with eCRF data entry at every 4 months. All patients will be treated with a one-month starting dose followed by 23 monthly maintenance doses for a duration of 672 days. The primary endpoints will be evaluated after 24 treatment months.

In total, 25 visits are scheduled for all patients.

Eligibility criteria: Inclusion Criteria:

* Able to read and write, understand instructions related to trial procedures and give written informed consent before any trial-related activity is performed
* Histologically confirmed adenocarcinoma of the prostate (prostate cancer)
* Currently under hormonal management of prostate cancer with a GnRH agonist
* Confirmed biochemical PSA progression on GnRH agonist therapy, defined as ≥50% increase in PSA between 2 measurements, taken at least 1 week apart
* PSA ≥1.0 ng/ml
* ECOG score ≤2
* Able and willing to participate in the full duration of the clinical trial
* Male patient aged 18 years or older
* Life expectancy of at least 12 months

Exclusion Criteria:

* Prior treatment with chemotherapy, radiopharmaceuticals, estrogen, ketoconazole or other secondary hormonal treatments such as antiandrogens except for induction phase (\<3 months)
* History of dermatitis, lupus, eczema, psoriasis affecting area used for Degarelix injections
* Allergy to Degarelix or its components
* Has a clinically significant disorder (other than prostate cancer) including, but not limited to, renal, haematological, gastrointestinal, endocrine, cardiac, neurological, or psychiatric disease, and alcohol or drug abuse or any other condition, which may affect the patient's health or the outcome of the trial as judged by the Investigator
* Has a history of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
* Has a history of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema
* Has a mental incapacity or language barrier precluding adequate understanding or co operation

Primary outcomes:
measure: Testosterone Suppression
timeFrame: Two Years after first dose of degarelix.
Secondary outcomes:
measure: Hormone Levels
timeFrame: Two Years after first dose of degarelix.
measure: PSA Response
timeFrame: Two Years after first dose of degarelix.
measure: PSA Failure
timeFrame: Two Years after first dose of degarelix.
measure: PSA Doubling Time
timeFrame: Two Years after first dose of degarelix.
measure: Time to Metastases
timeFrame: Two Years after first dose of degarelix.
measure: Time to Chemotherapy
timeFrame: Two Years after first dose of degarelix.
measure: Time to Anti-Androgen use
timeFrame: Two Years after first dose of degarelix.
measure: Patient Performance Status
timeFrame: Two Years after first dose of degarelix.
Other outcomes:
Locations:
city: Abbotsford
country: Canada
facility: Exdeo Clinical Research Inc.
state: British Columbia
city: Kelowna
country: Canada
facility: Southern Interior Medical Research Inc.
state: British Columbia
city: Surrey
country: Canada
facility: Andreou Research
state: British Columbia
city: Victoria
country: Canada
facility: Dr. Steinhoff Clinical Research
state: British Columbia
city: Barrie
country: Canada
facility: The Male/Female Health and Research Centre
state: Ontario
city: Brampton
country: Canada
facility: Jonathan Giddens Medicine Professional Corporation
state: Ontario
city: Brantford
country: Canada
facility: Brantford Urology Research
state: Ontario
city: Burlington
country: Canada
facility: G. Kenneth Jansz Medicine Professional Corporation
state: Ontario
city: Guelph
country: Canada
facility: Guelph Urology Associates
state: Ontario
city: Newmarket
country: Canada
facility: Mor Urology Inc.
state: Ontario
city: North York
country: Canada
facility: Toronto Urology Clinical Study Group
state: Ontario
city: Oakville
country: Canada
facility: The Fe/Male Health Centres
state: Ontario
city: Owen Sound
country: Canada
facility: 2150935 Ontario Inc.
state: Ontario
city: Scarborough
country: Canada
facility: 643094 Ontario Inc.
state: Ontario
city: Toronto
country: Canada
facility: Stanley Flax Medical Professional Corporation
state: Ontario
city: Greenfield Park
country: Canada
facility: Urology South Shore Research Inc.
state: Quebec
city: Laval
country: Canada
facility: Urolaval
state: Quebec
Study officials:
affiliation: CMX Research
name: Richard Casey, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Queens University
name: Alvaro Morales, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fontana D, Mari M, Martinelli A, Boccafoschi C, Magno C, Turriziani M, Maymone SS, Cunico SC, Zanollo A, Montagna G, Frongia M, Jacobellis U. 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot) in advanced prostate cancer: results from an Italian, open, multicenter trial. Urol Int. 2003;70(4):316-20. doi: 10.1159/000070142.
citation: Gittelman M, Pommerville PJ, Persson BE, Jensen JK, Olesen TK; Degarelix Study Group. A 1-year, open label, randomized phase II dose finding study of degarelix for the treatment of prostate cancer in North America. J Urol. 2008 Nov;180(5):1986-92. doi: 10.1016/j.juro.2008.07.033. Epub 2008 Sep 17.
citation: Jocham D. Leuprorelin three-month depot in the treatment of advanced and metastatic prostate cancer: long-term follow-up results. Urol Int. 1998;60 Suppl 2:18-24; discussion 35. doi: 10.1159/000056547.
citation: Khan MS, O'Brien A. An evaluation of pharmacokinetics and pharmacodynamics of leuprorelin acetate 3M-depot in patients with advanced and metastatic carcinoma of the prostate. Urol Int. 1998;60(1):33-40. doi: 10.1159/000030200.
citation: Morote J, Orsola A, Planas J, Trilla E, Raventos CX, Cecchini L, Catalan R. Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy. J Urol. 2007 Oct;178(4 Pt 1):1290-5. doi: 10.1016/j.juro.2007.05.129. Epub 2007 Aug 14.
citation: Van Poppel H, Tombal B, de la Rosette JJ, Persson BE, Jensen JK, Kold Olesen T. Degarelix: a novel gonadotropin-releasing hormone (GnRH) receptor blocker--results from a 1-yr, multicentre, randomised, phase 2 dosage-finding study in the treatment of prostate cancer. Eur Urol. 2008 Oct;54(4):805-13. doi: 10.1016/j.eururo.2008.04.065. Epub 2008 May 8.
citation: Zinner NR, Bidair M, Centeno A, Tomera K. Similar frequency of testosterone surge after repeat injections of goserelin (Zoladex) 3.6 mg and 10.8 mg: results of a randomized open-label trial. Urology. 2004 Dec;64(6):1177-81. doi: 10.1016/j.urology.2004.07.033.