A Degarelix Trial in Patients With Prostate Cancer

Study Overview
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Brief Summary
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A phase III extension trial comparing the efficacy and safety of degarelix 3 month depot with the established therapy Zoladex 3 month implant in patients with prostate cancer.

Detailed Description
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CS35A was an open-label, multicentre, comparative non-inferiority extension trial to the Phase 3 CS35 trial (NCT00946920). In the main CS35 trial, participants were randomised 2:1 to treatment with degarelix or goserelin, respectively. All participants who completed the main CS35 trial after initiation of the CS35A trial were eligible to enrol into this extension trial, provided that their treatment could continue uninterrupted. Patients entering the CS35A trial continued with the same 3-monthly treatment as they received in CS35 (i.e. degarelix 480 mg or goserelin 10.8 mg). It was intended that patients enrolled in the CS35A trial would receive treatment with degarelix or goserelin at 3-month intervals for a period of 40 months (including 13 months' treatment in CS35). It was, however, decided to prematurely terminate the CS35A trial due to an insufficient number of patients being enrolled. Maximum exposure of treatment was 111 weeks (in both treatment arms). The baseline characteristics are based on the CS35A Full Analysis Set (FAS)defined as all participants who received at least one dose of degarelix or goserelin acetate during CS35A and had at least one efficacy assessment after dosing. All efficacy analyses were performed for the CS35/CS35A FAS defined as all participants who received at least one dose of degarelix or goserelin acetate during CS35 and had at least one efficacy assessment after dosing. All safety analyses were performed for the CS35/CS35A Safety analysis set, which included all patients who received at least one dose of degarelix or goserelin acetate during CS35.

Official Title
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An Open-label, Multi-Centre, Extension Trial, Evaluating the Long-Term Progression-Free Survival of Degarelix or Goserelin Three-Month Dosing Regimens in Patients With Prostate Cancer Requiring Androgen Deprivation Therapy

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Degarelix
* Drug: Goserelin acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has given written consent prior to any trial-related activity is performed. (A trial-related activity is defined as any procedure that would not have been performed during the normal management of the patient). Has completed the CS35 trial. Exclusion Criteria: Has been withdrawn from the CS35 trial. Has had end of trial visit in CS35 prior to approval of the CS35A protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Degarelix 240 mg/480 mg<br> | Drug: Degarelix<br>* The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. In the main CS35 trial, a starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the degarelix treated participants continued to receive degarelix 480 mg s.c. treatment every three months.<br>* Other names: FE200486;|
| Active Comparator: Goserelin acetate<br> | Drug: Goserelin acetate<br>* The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. In the main CS35 trial, an initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants in the main trial). In the CS35A extension trial, the participants received the same treatment as in the main trial ie the goserelin treated participants continued to receive goserelin acetate 10.8 mg s.c. implants every three months.<br>* Other names: Zoladex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hazard Ratio of Prostate-specific Antigen (PSA) Progression-free Survival (PFS) Failure Rates During 3 Years' Treatment Between Degarelix and Goserelin | PSA PFS failure is defined as either PSA failure (defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart) or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA-PFS. | From baseline to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hazard Ratio of PFS Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | PFS failure is defined as either PSA failure, introduction of additional therapy related to prostate cancer (radiation, anti-androgens or second-line treatment), or death, whichever is first. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PFS failure. | From baseline to 3 years | 
| Hazard Ratio of PSA Failure Rates During 3 Years Treatment Between Degarelix and Goserelin | PSA failure is defined as increase in serum PSA of 50%, and at least 5 ng/mL, compared to nadir, measured on two consecutive occasions at least 2 weeks apart. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no PSA failure. | From baseline to 3 years | 
| Hazard Ratio of Testosterone Escape Rates During 3 Years' Treatment Between Degarelix and Goserelin | Testosterone escape is defined as serum levels >0.5 ng/mL. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no testosterone escape. | From baseline to 3 years | 
| Hazard Ratio of the Rates of Introduction of Additional Therapy Related to Prostate Cancer During 3 Years' Treatment Between Degarelix and Goserelin | Additional therapy related to prostate cancer included radiation, anti-androgens and second-line treatment. The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of no additional therapy related to prostate cancer. | From baseline to 3 years | 
| Hazard Ratio of Mortality Rates During 3 Years' Treatment Between Degarelix and Goserelin | The number below present the unadjusted rates (estimated using the Kaplan-Meier method) of death. | From baseline to 3 years | 
| Serum Levels of Testosterone During 3 Years' Treatment With Degarelix or Goserelin | Median testosterone levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed. | Baseline and after 1, 6, 12, 19, and 22 months | 
| Serum Levels of Prostate-specific Antigen (PSA) During 3 Years' Treatment With Degarelix or Goserelin | Median PSA levels are presented as absolute values in nanograms per milliliter (ng/mL) at baseline and after 1, 6, 12, 19, and 22 months. One month equals 28 days. After 22 months, only a limited number of samples were analysed. | Baseline and after 1, 6, 12, 19, and 22 months |