Neoadjuvant Study Investigating Degarelix in Patients Suffering From Prostate Cancer

A Randomised, Parallel Arm, Open-label Trial Comparing Degarelix With Goserelin Plus Anti-androgen Flare Protection (Bicalutamide), in Terms of Prostate Size Reduction in Prostate Cancer Patients of Intermediate-to-high Risk, Who Require Neoadjuvant Hormone Therapy Prior to Radiotherapy (Curative Intent)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00833248

Enrollment

246

Registered

2009-02-02

Start date

2009-04-30

Completion date

2011-09-30

Last updated

2012-10-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Prostate Cancer

Brief summary

The purpose of this phase 3B trial was to see how well a new trial drug (degarelix) works in terms of reducing the size of the prostate volume in prostate cancer patients who were scheduled to undergo subsequent radiotherapy for treatment of their prostate cancer. Prior to receiving radiotherapy, it is recommended that patients with intermediate to high risk prostate cancer are pre-treated with hormone therapy (so-called neoadjuvant therapy) which is known to reduce the size of the prostate and thereby decrease the required radiation field and enable a more safe and effective treatment. In this trial, participants were randomly selected (like flipping a coin) to receive either degarelix given alone or a standard hormone therapy (combination of goserelin and bicalutamide. The treatment was given for three months and the prostate size was measured by ultra sound at the beginning and at the end of the trial. The participants were required to come to the clinic for 5 or 6 visits during the three months.

Interventions

DRUGDegarelix

The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.

DRUGGoserelin

Goserelin implants (3.6 mg) were inserted s.c. into the abdominal wall every 28 days. The first dose was administered on Day 3. The second and third doses of goserelin were administered on Days 31 and 59, respectively.

DRUGBicalutamide

On Day 0, participants began once-daily per-oral (p.o.) treatment with bicalutamide (50 mg) as anti-androgen flare protection; this treatment continued for 14 days after the first dose of goserelin.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Patient has given written informed consent before any trial-related activity is performed. * Has a confirmed prostate cancer in which this type of treatment is needed.

Exclusion criteria

* Previous treatment for prostate cancer * Previous trans-urethral resection of the prostate * Patients who are lymph node positive or have other metastatic disease * Use of urethral catheter * Current treatment with a 5-alpha reductase inhibitor or α-adrenoceptor antagonist. * History of severe untreated asthma, anaphylactic reactions, or severe urticaria and/or angioedema. * Hypersensitivity towards any component of the investigational product * Other previous cancers within the last five years with the exception of prostate cancer and some types of skin cancer. * Certain risk factors for abnormal heart rhythms/QT prolongation (corrected QT interval over 450 msec., Torsades de Pointes or use of certain medications with potential risk) * Clinical disorders other than prostate cancer including but not limited to renal, haematological, gastrointestinal, endocrine, cardiac, neurological, psychiatric disease, alcohol or drug abuse or other conditionals as judged by the investigator.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)	After treatment of 12 weeks compared to Baseline	TRUS is a method of measuring the size of the prostate.
Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)	After treatment of 12 weeks compared to Baseline	TRUS is a method of measuring the size of the prostate.

Secondary

Measure	Time frame	Description
Change From Baseline in Serum Prostate-Specific Antigen (PSA) Levels During the Study	After treatment of 4, 8, and 12 weeks compared to Baseline	—
Change From Baseline in Serum Oestradiol Levels During the Study	After treatment of 4, 8, and 12 weeks compared to Baseline	—
Change From Baseline in Total International Prostate Symptom Score (IPSS) at Week 4, 8, and 12	After treatment of 4, 8, and 12 weeks compared to Baseline	The IPSS is a tool commonly used to assess the severity of lower urinary tract symptoms (LUTS), and to monitor the progress of the disease once treatment has been initiated. The participant completes a questionnaire containing 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5. The total score is then classified according to the following scale: 0 to 7 = mildly symptomatic; 8 to 19 = moderately symptomatic; and 20 to 35 = severely symptomatic.
Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight	Baseline to 12 weeks of treatment	This outcome measure included incidence of markedly abnormal changes in blood pressure (systolic and diastolic), pulse, and body weight. The table presents the number of participants with normal baseline and at least one post-baseline markedly abnormal value.
Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables	Baseline to 12 weeks of treatment	The figures present the number of participants who had abnormal (defined as above upper limit of normal range (ULN)) levels of safety laboratory variables. Only the laboratory variables that had at least one percentage of participants in either group with abnormal value are presented, more variables were included in the study.
Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit	After treatment of 4, 8, and 12 weeks compared to Baseline	The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6').
Change From Baseline in Serum Testosterone Levels During the Study	After treatment of 4, 8, and 12 weeks compared to Baseline	—

Countries

France, Germany, Greece, Netherlands, Spain, United Kingdom, United States

Participant flow

Recruitment details

The participants were recruited by outpatient urologists, radiotherapists or oncologists. A total of 240 patients were to be randomised in a 3:1 ratio to one of two treatment groups (180 participants were to be treated with degarelix; 60 participants were to be treated with goserelin+bicalutamide). The recruitment period was April 2009 - June 2011.

Participants by arm

Arm	Count
Degarelix 240 mg/80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The second and third doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections on Days 28 and 56, respectively.	180
Goserelin (3.6 mg) + Bicalutamide (50 mg) On Day 0, the participants began once-daily oral (p.o.) treatment with bicalutamide as anti-androgen flare protection. This treatment continued for 2 weeks after the first dose of goserelin (i.e. 17 days in total). On Day 3, the first goserelin implant was inserted s.c. into the abdominal wall. The second and third doses of goserelin were administered on Days 31 and 59, respectively.	64
Total	244

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	3	0
Overall Study	Protocol Violation	1	2
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	Total	Degarelix 240 mg/80 mg	Goserelin (3.6 mg) + Bicalutamide (50 mg)
Age Continuous	70.6 years STANDARD_DEVIATION 6.25	70.6 years STANDARD_DEVIATION 6.37	70.8 years STANDARD_DEVIATION 5.96
Body Mass Index	27.5 kilogram per square meter STANDARD_DEVIATION 3.93	27.8 kilogram per square meter STANDARD_DEVIATION 3.99	26.8 kilogram per square meter STANDARD_DEVIATION 3.69
Body Weight	82.9 kilogram STANDARD_DEVIATION 13.8	83.6 kilogram STANDARD_DEVIATION 14.2	80.9 kilogram STANDARD_DEVIATION 12.4
Gleason Score Gleason Score 2-6	53 participants	41 participants	12 participants
Gleason Score Gleason Score 7	139 participants	97 participants	42 participants
Gleason Score Gleason Score 8-10	52 participants	42 participants	10 participants
Prostate Volume	51.3 milliliter STANDARD_DEVIATION 19.9	50.9 milliliter STANDARD_DEVIATION 20.3	52.5 milliliter STANDARD_DEVIATION 18.8
Quality of Life (QoL) Related to Urinary Symptoms	2.19 scores on a scale STANDARD_DEVIATION 1.62	2.27 scores on a scale STANDARD_DEVIATION 1.63	1.94 scores on a scale STANDARD_DEVIATION 1.56
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Black or African American	18 Participants	15 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	224 Participants	163 Participants	61 Participants
Region of Enrollment France	82 participants	60 participants	22 participants
Region of Enrollment Germany	13 participants	9 participants	4 participants
Region of Enrollment Greece	7 participants	5 participants	2 participants
Region of Enrollment Netherlands	13 participants	11 participants	2 participants
Region of Enrollment Spain	12 participants	9 participants	3 participants
Region of Enrollment United Kingdom	56 participants	41 participants	15 participants
Region of Enrollment United States	61 participants	45 participants	16 participants
Serum Oestradiol Levels	1.9 nanograms per deciliter	1.9 nanograms per deciliter	1.9 nanograms per deciliter
Serum Prostate-Specific Antigen (PSA) Levels	9.95 nanograms per millilter	10 nanograms per millilter	9.75 nanograms per millilter
Serum Testosterone Levels	4.06 nanograms per milliliter	3.92 nanograms per milliliter	4.42 nanograms per milliliter
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	244 Participants	180 Participants	64 Participants
Stage of Prostate Cancer Localized	152 participants	111 participants	41 participants
Stage of Prostate Cancer Locally Advanced	83 participants	63 participants	20 participants
Stage of Prostate Cancer Metastatic	0 participants	0 participants	0 participants
Stage of Prostate Cancer Not Classifiable	9 participants	6 participants	3 participants
Total International Prostate Symptom Score (IPSS)	9.23 scores on a scale STANDARD_DEVIATION 6.61	9.5 scores on a scale STANDARD_DEVIATION 6.71	8.46 scores on a scale STANDARD_DEVIATION 6.3

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	158 / 181	53 / 64
serious Total, serious adverse events	7 / 181	0 / 64

Outcome results

Primary

Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)

TRUS is a method of measuring the size of the prostate.

Time frame: After treatment of 12 weeks compared to Baseline

Population: FAS, Observed Case (OC) i.e. only participants with a reported value were included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
Degarelix 240 mg/80 mg	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)	-36.0 milliliter	Standard Deviation 14.5
Goserelin (3.6 mg) + Bicalutamide (50 mg)	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Full Analysis Set)	-35.3 milliliter	Standard Deviation 16.7

Comparison: FAS. Estimates from analysis of variance with treatment as factors and baseline IPSS and baseline Prostate volume as covariates.p-value: 0.894295% CI: [-4.74, 4.14]ANCOVA

Primary

Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)

TRUS is a method of measuring the size of the prostate.

Time frame: After treatment of 12 weeks compared to Baseline

Population: FAS, OC.

Arm	Measure	Value (MEAN)	Dispersion
Degarelix 240 mg/80 mg	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)	-36.2 milliliter	Standard Deviation 14.5
Goserelin (3.6 mg) + Bicalutamide (50 mg)	Change From Baseline in Prostate Size Based on Trans Rectal Ultra Sound (TRUS) at Week 12 (Per Protocol Analysis Set)	-35.4 milliliter	Standard Deviation 16.9

Comparison: PP analysis set. Estimates from analysis of variance with treatment as factors and baseline IPSS and baseline Prostate volume as covariates.p-value: 0.912395% CI: [-5.05, 4.52]ANCOVA

Secondary

Change From Baseline in Quality of Life (QoL) Related to Urinary Symptoms at Each Visit

The IPSS questionnaire included an additional single question to assess the participant's QoL in relation to his urinary symptoms. The question was: 'If you were to spend the rest of your life with your urinary condition the way it is now, how would you feel about that?' The possible answers to this question ranged from 'delighted' (a score of '0') to 'terrible' (a score of '6').