Trial Outcomes & Findings for Observational Program to Assess Use of Intermittent Adjuvant Deprivation Therapy With Leuprorelin (Lucrin Depot) in Patients With Advanced Prostate Cancer (PCa) in Russia (NCT NCT01320735)

NCT ID: NCT01320735

Last Updated: 2015-07-08

Results Overview

Total duration of leuprorelin Intermittent Androgen Deprivation (IAD) regimen was calculated as (Last dose date of Leuprorelin minus first dose date plus 1)/30.4. If the stop date of leuprorelin administration was missing then the date of last attended visit was used. Total duration may include gaps between the cycles. The data are reported as mean months +/- standard deviation.

• Recruitment status: COMPLETED
• Target enrollment: 300 participants
• Primary outcome timeframe: 24 months
• Results posted on: 2015-07-08

Participant Flow

From 300 participants enrolled in the study, data of 17 participants from one of the sites were excluded from analysis because of the impossibility to contact the investigator for data clarification. Hence 283 participants were included in the analysis.

Participant milestones

Measure	Advanced Prostate Cancer (PCa) Participants with advanced PCa
Overall Study STARTED	300
Overall Study COMPLETED	194
Overall Study NOT COMPLETED	106

Reasons for withdrawal

Measure	Advanced Prostate Cancer (PCa) Participants with advanced PCa
Overall Study Adverse Event	3
Overall Study Withdrawal by Subject	3
Overall Study Lost to Follow-up	13
Overall Study Administrative Reason	6
Overall Study Progression/Hormone-Refractory Pca	55
Overall Study Protocol Violation	1
Overall Study Other	1
Overall Study No Decrease of Prostate Specific Antigen	7
Overall Study Investigator Unable to be Contacted	17

Baseline Characteristics

Observational Program to Assess Use of Intermittent Adjuvant Deprivation Therapy With Leuprorelin (Lucrin Depot) in Patients With Advanced Prostate Cancer (PCa) in Russia

Baseline characteristics by cohort

Measure	Advanced PCa n=283 Participants Participants with advanced PCa
Age, Continuous	65.4 Years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	283 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 months

Population: Data are of measurements collected from the safety analysis set, defined as all participants who signed an informed consent form and were administered at least one dose of leuprorelin.

Total duration of leuprorelin Intermittent Androgen Deprivation (IAD) regimen was calculated as (Last dose date of Leuprorelin minus first dose date plus 1)/30.4. If the stop date of leuprorelin administration was missing then the date of last attended visit was used. Total duration may include gaps between the cycles. The data are reported as mean months +/- standard deviation.

Outcome measures

Measure	Advanced PCa n=283 Participants Participants with advanced PCa
Mean Duration of Leuprorelin Exposure All participants	19.74 Months Standard Deviation 6.39
Mean Duration of Leuprorelin Exposure Participants with no progression (N=227)	21.25 Months Standard Deviation 5.31
Mean Duration of Leuprorelin Exposure Participants with progression (N=56)	13.62 Months Standard Deviation 6.79

PRIMARY outcome

Timeframe: 24 months

Population: Data are of measurements collected from the safety analysis set, defined as all participants who signed an informed consent form and were administered at least one dose of leuprorelin.

Duration of each cycle of leuprorelin IAD regimen was calculated as (Date of last dose of cycle of leuprorelin minus start date of cycle plus 1)/30.4. The data are reported as mean months +/- standard deviation.

Outcome measures

Measure	Advanced PCa n=283 Participants Participants with advanced PCa
Mean Duration of Each Leuprorelin Cycle All Participants: Cycle 1 (N=282)	7.63 Months Standard Deviation 1.73
Mean Duration of Each Leuprorelin Cycle All Participants: Cycle 2 (N=238)	5.60 Months Standard Deviation 2.21
Mean Duration of Each Leuprorelin Cycle All Participants: Cycle 3 (N=61)	4.64 Months Standard Deviation 1.63
Mean Duration of Each Leuprorelin Cycle All Participants: Cycle 4 (N=7)	3.44 Months Standard Deviation 1.09
Mean Duration of Each Leuprorelin Cycle All Participants: Cycle 5 (N=1)	3.30 Months Standard Deviation NA Not applicable as only 1 participant was assessed.
Mean Duration of Each Leuprorelin Cycle Participants with No Progression: Cycle 1 (N=226)	7.68 Months Standard Deviation 1.49
Mean Duration of Each Leuprorelin Cycle Participants with No Progression: Cycle 2 (206)	5.70 Months Standard Deviation 2.08
Mean Duration of Each Leuprorelin Cycle Participants with No Progression: Cycle 3 (N=52)	4.72 Months Standard Deviation 1.55
Mean Duration of Each Leuprorelin Cycle Participants with No Progression: Cycle 4 (N=7)	3.44 Months Standard Deviation 1.09
Mean Duration of Each Leuprorelin Cycle Participants with No Progression: Cycle 5 (N=1)	3.30 Months Standard Deviation NA Not applicable as only 1 participant was assessed.
Mean Duration of Each Leuprorelin Cycle Participants with Progression: Cycle 1 (N=56)	7.43 Months Standard Deviation 2.49
Mean Duration of Each Leuprorelin Cycle Participants with Progression: Cycle 2 (N=32)	4.96 Months Standard Deviation 2.84
Mean Duration of Each Leuprorelin Cycle Participants with Progression: Cycle 3 (N=9)	4.19 Months Standard Deviation 2.08

PRIMARY outcome

Timeframe: 24 months

Population: Data are of measurements collected from the safety analysis set, defined as all participants who signed an informed consent form and were administered at least one dose of leuprorelin. However, one participant started continuous hormone therapy and was not included in the analysis.

The Participants were on IAD regimen and the data are reported as number of cycles with full range.

Outcome measures

Measure	Advanced PCa n=282 Participants Participants with advanced PCa
Median Number of Leuprorelin Cycles	2 Cycles Interval 1.0 to 5.0

PRIMARY outcome

Timeframe: 24 months

Population: Data are of measurements collected from the safety analysis set, defined as all participants who signed an informed consent form and were administered at least one dose of leuprorelin.

The data are reported as percentage of participants.

Outcome measures

Measure	Advanced PCa n=283 Participants Participants with advanced PCa
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Overall Study	31.4 Percentage of participants
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Cycle 1	15.2 Percentage of participants
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Cycle 2 (N=240)	14.6 Percentage of participants
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Cycle 3 (N=119)	62.2 Percentage of participants
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Cycle 4 (N=17)	64.7 Percentage of participants
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen Cycle 5 (N=1)	0.0 Percentage of participants

PRIMARY outcome

Timeframe: 24 months

Population: Data are of measurements collected from the safety analysis set, defined as all participants who signed an informed consent form and were administered at least one dose of leuprorelin.

The data are reported as number of participants.

Outcome measures

Measure	Advanced PCa n=283 Participants Participants with advanced PCa
Number of Participants Who Switched to IAD Regimen by Visit Visit 2 After One Year (N=257)	237 Participants
Number of Participants Who Switched to IAD Regimen by Visit Visit 3 After Two Years (N=225)	197 Participants

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Data are of measurements collected from the full analysis set, defined as all participants who received at least one dose of leuprorelin, signed informed consent, did not violate any inclusion/exclusion criteria and attended at least one post-baseline visit.

Progression to HRPC was defined as castrate serum testosterone less than 50 ng/dL or 1.7 nmol/L plus either; biochemical progression (three consecutive rises in prostate specific antigen (PSA) levels one week apart resulting in two 50 % increases over the nadir, with PSA greater than 2 ng/ml) or radiological progression (the appearance of two or more new bone lesions on bone scan or enlargement of a soft tissue lesion using Response Evaluation Criteria in Solid Tumors (RECIST). Data are reported as number of participants with HRPC.

Outcome measures

Measure	Advanced PCa n=255 Participants Participants with advanced PCa
Number of Participants Who Progressed to Hormone Refractory Prostate Cancer (HRPC) All Participants	36 Participants
Number of Participants Who Progressed to Hormone Refractory Prostate Cancer (HRPC) Participants who started IAD	28 Participants
Number of Participants Who Progressed to Hormone Refractory Prostate Cancer (HRPC) Participants who did not start IAD	8 Participants

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Data are of measurements collected from the full analysis set, defined as all participants who received at least one dose of leuprorelin, signed informed consent, did not violate any inclusion/exclusion criteria and attended at least one post-baseline visit.

Time to progression of HRPC was calculated as date of progression minus date of first dose of leuprorelin. The data are reported as median (full range).

Outcome measures

Measure	Advanced PCa n=255 Participants Participants with advanced PCa
Median Time to Progression of HRPC All Participants (N=36)	17.12 Months Interval 3.0 to 24.8
Median Time to Progression of HRPC Participants who started IAD (N=28)	19.10 Months Interval 5.0 to 24.8
Median Time to Progression of HRPC Participants who did not start IAD (N=8)	8.11 Months Interval 3.0 to 15.4

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Data are of measurements of participants who did not start on IAD regimen.

Time to progression of HRPC was calculated as date of progression minus date of first dose of leuprorelin. A Kaplan-Meier estimate of median time to progression to HRPC and 25% and 75% quartiles along with the 95% confidence interval for median were assessed.

Outcome measures

Measure	Advanced PCa n=20 Participants Participants with advanced PCa
Median Time to Progression of HRPC in Participants Not Started on IAD Regimen	12.8 Months Interval 12.8 to 15.4

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Participants who died while on study were used for analysis.

Time to survival was estimated as time from start of leuprorelin up to study completion/discontinuation from the study or date of death. The data are reported as median months with full range.

Outcome measures

Measure	Advanced PCa n=4 Participants Participants with advanced PCa
Median Survival Time All Participants (N=4)	18.94 Months Interval 11.8 to 24.8
Median Survival Time Participants who started IAD (N=2)	24.44 Months Interval 24.1 to 24.8
Median Survival Time Participants who did not start IAD (N=2)	12.76 Months Interval 11.8 to 13.8

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Data are of measurements collected from participants who started IAD.

Duration of each leuprorelin free period was calculated as (Date of first dose of leuprorelin [cycle N+1] minus last dose date [cycle N] minus 1)/30.4. If date of last dose of leuprorelin was before the date of study completion/discontinuation then the last leuprorelin free period was calculated as (Date of discontinuation/study completion minus last leuprorelin dose date)/30.4. The data are reported as mean months +/- standard deviation.

Outcome measures

Measure	Advanced PCa n=243 Participants Participants with advanced PCa
Mean Duration of Treatment-off Time in IAD Regimen	7.12 Months Standard Deviation 2.61

SECONDARY outcome

Timeframe: Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Population: Data are of measurements collected from participants who started IAD.

The total duration of leuprorelin free period was calculated as the sum of all leuprorelin free periods. The data are reported as median percentage of time off-treatment with full range.

Outcome measures

Measure	Advanced PCa n=243 Participants Participants with advanced PCa
Median Percentage of Time Off-treatment During 2 Years IAD Regimen	33.45 Percentage of time off-treatment Interval 0.0 to 67.6

OTHER_PRE_SPECIFIED outcome

Timeframe: At least 6-9 months after Baseline (enrollment)

Population: Data are of measurements collected from participants who started IAD.

Time period between first injection of leuprorelin and stopping of treatment due to appropriate decrease of PSA as defined in the protocol. The data are reported as mean months +/- standard deviation.

Outcome measures

Measure	Advanced PCa n=240 Participants Participants with advanced PCa
Duration of IAD Regimen Induction Phase All participants (N=240)	7.70 Months Standard Deviation 1.25
Duration of IAD Regimen Induction Phase Participants with no progression (N=207)	7.75 Months Standard Deviation 1.13
Duration of IAD Regimen Induction Phase Participants with progression (N=33)	7.32 Months Standard Deviation 1.79

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Data are of measurements collected from participants who started IAD.

The data are reported as number of participants.

Outcome measures

Measure	Advanced PCa n=243 Participants Participants with advanced PCa
Number of Participants Who Received IAD Regimen During the Study All participants	243 Participants
Number of Participants Who Received IAD Regimen During the Study Participants with no progression	210 Participants
Number of Participants Who Received IAD Regimen During the Study Participants with progression	33 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 24 months

Population: Data are of measurements collected from participants who started IAD.

The data are reported as number of participants.

Outcome measures

Measure	Advanced PCa n=243 Participants Participants with advanced PCa
Number of Participants Who Continued to Take Leuprorelin in IAD Regimen by the End of the Study All participants	69 Participants
Number of Participants Who Continued to Take Leuprorelin in IAD Regimen by the End of the Study Participants with no progression (N=210)	68 Participants
Number of Participants Who Continued to Take Leuprorelin in IAD Regimen by the End of the Study Participants with progression (N=33)	1 Participants

Adverse Events

Advanced PCa

Serious events: 13 serious events

Other events: 73 other events

Deaths: 0 deaths

Serious adverse events

Measure	Advanced PCa n=283 participants at risk Participants with advanced PCa
General disorders DISEASE PROGRESSION	2.5% 7/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Cardiac disorders CARDIAC DISORDER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Cardiac disorders MYOCARDIAL INFARCTION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CANCER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Renal and urinary disorders URINARY RETENTION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period

Other adverse events

Measure	Advanced PCa n=283 participants at risk Participants with advanced PCa
Infections and infestations NASOPHARYNGITIS	11.0% 31/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Infections and infestations BRONCHITIS	5.7% 16/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Infections and infestations PNEUMONIA	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
General disorders DISEASE PROGRESSION	4.6% 13/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
General disorders FATIGUE	1.8% 5/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
General disorders ASTHENIA	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
General disorders OEDEMA	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Vascular disorders HOT FLUSH	4.2% 12/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Vascular disorders HYPERTENSION	0.71% 2/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Reproductive system and breast disorders GYNAECOMASTIA	2.1% 6/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Reproductive system and breast disorders BREAST ENLARGEMENT	1.4% 4/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Reproductive system and breast disorders ACQUIRED HYDROCELE	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Reproductive system and breast disorders ERECTILE DYSFUNCTION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Gastrointestinal disorders GASTRITIS	1.1% 3/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Gastrointestinal disorders PEPTIC ULCER	0.71% 2/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Gastrointestinal disorders GASTRIC ULCER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Skin and subcutaneous tissue disorders DERMATITIS	1.8% 5/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Metabolism and nutrition disorders DIABETES MELLITUS	1.1% 3/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Respiratory, thoracic and mediastinal disorders COUGH	1.1% 3/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Cardiac disorders CARDIAC DISORDER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Cardiac disorders MYOCARDIAL INFARCTION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Musculoskeletal and connective tissue disorders ARTHRITIS	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Musculoskeletal and connective tissue disorders ARTHROPATHY	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) PROSTATE CANCER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Neoplasms benign, malignant and unspecified (incl cysts and polyps) RENAL CANCER	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Hepatobiliary disorders CHOLECYSTITIS ACUTE	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Injury, poisoning and procedural complications RIB FRACTURE	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Psychiatric disorders DEPRESSION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Renal and urinary disorders URINARY RETENTION	0.35% 1/283 • From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period

Additional Information

Global Medical Services

AbbVie (prior sponsor, Abbott)

Phone: 800-633-9110

Results disclosure agreements

• Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
• Publication restrictions are in place

Restriction type: OTHER