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

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01320735
• Collaborator: Almedis (Industry)
• Enrollment: 300
• Duration (Months): 38.9

Study Details

Study Description

Brief Summary

The objective of this study was to describe treatment patterns of leuprorelin over 2 years using an intermittent, adjuvant regimen in participants with advanced prostate cancer (PCa)

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer

Detailed Description

Participants started hormone treatment with Leuprorelin 3.75 mg once every 28 days, subcutaneously (SC) or intramuscularly (IM). Duration of induction therapy was at least 6 months (6-9 months) during which PSA and testosterone levels were measured every 3 months. When PSA decreased by greater than 90% from baseline (PSA less than 10 ng/ml) or became lower than 4.0 ng/ml (for 2 consecutive measurements made at least 2 weeks apart) the participants were included into intermittent hormone therapy regimen group (IAD). Participants with PSA decrease not achieved greater than 90% or less than or equal to 4.0 ng/ml were given either continuous hormone therapy (CAD) or chemotherapy.

Therapy was stopped if participants had PSA decrease greater than 90% from baseline or values less than 4.0 ng/ml after 6-9 months of continuous hormone therapy. PSA and testosterone were measured every 4 weeks. If PSA became greater than or equal to 10.0 ng/ml, hormone therapy was resumed until PSA was less than 4.0 ng/ml for 2 consecutive measurements made at least 2 weeks apart. Duration of hormonal therapy cycle was at least 3 months. Then intermittent treatment was performed according to a similar scheme. PSA and testosterone levels were determined every 12 weeks when hormone therapy was administered and every 4 weeks after it was stopped. The treatment was carried out for 2 years or until Hormone Refractory Prostate Cancer (HRPC) developed.

Study Design

• Study Type: Observational
• Actual Enrollment: 300 participants
• Time Perspective: Prospective
• Official Title: Prospective, Multi-Center, Observational Program to Assess Routine Use of Intermittent Adjuvant Deprivation Therapy With Lucrin Depot in Patients With Advanced Prostate Cancer in the Russian Federation
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: May 1, 2014
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Advanced PCa Participants with advanced PCa

Outcome Measures

Primary Outcome Measures

1. Mean Duration of Leuprorelin Exposure [24 months]

   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.

2. Mean Duration of Each Leuprorelin Cycle [24 months]

   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.

3. Median Number of Leuprorelin Cycles [24 months]

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

4. Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen [24 months]

   The data are reported as percentage of participants.

5. Number of Participants Who Switched to IAD Regimen by Visit [24 months]

   The data are reported as number of participants.

Secondary Outcome Measures

1. Number of Participants Who Progressed to Hormone Refractory Prostate Cancer (HRPC) [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year 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.

2. Median Time to Progression of HRPC [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year 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).

3. Median Time to Progression of HRPC in Participants Not Started on IAD Regimen [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit]

   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.

4. Median Survival Time [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit]

   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.

5. Mean Duration of Treatment-off Time in IAD Regimen [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit]

   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.

6. Median Percentage of Time Off-treatment During 2 Years IAD Regimen [Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit]

   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.

Other Outcome Measures

1. Duration of IAD Regimen Induction Phase [At least 6-9 months after Baseline (enrollment)]

   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.

2. Number of Participants Who Received IAD Regimen During the Study [24 months]

   The data are reported as number of participants.

3. Number of Participants Who Continued to Take Leuprorelin in IAD Regimen by the End of the Study [24 months]

   The data are reported as number of participants.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Histologically confirmed advanced PCa meeting the following criteria:

2. Any Tumor, Node 1, Metastasis 0

3. Any Tumor, Node 0, Metastasis 1 [according to Tumor Node Metastasis classification 2009]

4. Participants planned for administration of leuprorelin

5. World Health Organization status 0-1

6. Life expectancy at least 2 years

Exclusion Criteria:

1. Contraindications to administration of leuprorelin:

2. Hypersensitivity to Leuprorelin similar products of protein origin or any of the excipients in drug product composition

3. Surgical castration

4. Hormone-refractory PCa

5. Presence of another malignant tumor (except skin cancer)

6. Previous administration of hormone therapy with gonadotropin-releasing hormone agonists or antiandrogens

7. Previous administration of radiotherapy or chemotherapy course within 1 month

8. Testosterone level less than or equal to 50 ng/dl (less than or equal to 1.7 mmol/l) at time of inclusion

9. Extremely high level of PSA (greater than or equal to 1000 ng/ml)

10. Other severe diseases in stage of decompensation

11. Other contraindications, that make the participant's participation impossible (by investigator judgment)

12. Previous enrollment in the present program

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)
• Almedis

Investigators

• Study Director: Andrey Strugovshchikov, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01320735
• Other Study ID Numbers: P12-763
• First Posted: Mar 22, 2011
• Last Update Posted: Jul 8, 2015
• Last Verified: Jun 1, 2015

• Keywords provided by AbbVie (prior sponsor, Abbott): Lucrin Depot; intermittent adjuvant regimen; advanced prostate cancer; Leuprorelin
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Advanced Prostate Cancer (PCa)
Arm/Group Description	Participants with advanced PCa
Period Title: Overall Study
STARTED	300
COMPLETED	194
NOT COMPLETED	106

Baseline Characteristics

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Overall Participants	283
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.4 (6.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	283 100%

Outcome Measures

1. Other Pre-specified Outcome

Title	Duration of IAD Regimen Induction Phase
Description	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.
Time Frame	At least 6-9 months after Baseline (enrollment)

Outcome Measure Data

Analysis Population Description

Data are of measurements collected from participants who started IAD.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	240
All participants (N=240)	7.70 (1.25)
Participants with no progression (N=207)	7.75 (1.13)
Participants with progression (N=33)	7.32 (1.79)

2. Primary Outcome

Title	Mean Duration of Leuprorelin Exposure
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	283
All participants	19.74 (6.39)
Participants with no progression (N=227)	21.25 (5.31)
Participants with progression (N=56)	13.62 (6.79)

3. Primary Outcome

Title	Mean Duration of Each Leuprorelin Cycle
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	283
All Participants: Cycle 1 (N=282)	7.63 (1.73)
All Participants: Cycle 2 (N=238)	5.60 (2.21)
All Participants: Cycle 3 (N=61)	4.64 (1.63)
All Participants: Cycle 4 (N=7)	3.44 (1.09)
All Participants: Cycle 5 (N=1)	3.30 (NA)
Participants with No Progression: Cycle 1 (N=226)	7.68 (1.49)
Participants with No Progression: Cycle 2 (206)	5.70 (2.08)
Participants with No Progression: Cycle 3 (N=52)	4.72 (1.55)
Participants with No Progression: Cycle 4 (N=7)	3.44 (1.09)
Participants with No Progression: Cycle 5 (N=1)	3.30 (NA)
Participants with Progression: Cycle 1 (N=56)	7.43 (2.49)
Participants with Progression: Cycle 2 (N=32)	4.96 (2.84)
Participants with Progression: Cycle 3 (N=9)	4.19 (2.08)

4. Secondary Outcome

Title	Number of Participants Who Progressed to Hormone Refractory Prostate Cancer (HRPC)
Description	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.
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	255
All Participants	36 12.7%
Participants who started IAD	28 9.9%
Participants who did not start IAD	8 2.8%

5. Primary Outcome

Title	Median Number of Leuprorelin Cycles
Description	The Participants were on IAD regimen and the data are reported as number of cycles with full range.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	282
Median (Full Range) [Cycles]	2

6. Secondary Outcome

Title	Median Time to Progression of HRPC
Description	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).
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	255
All Participants (N=36)	17.12
Participants who started IAD (N=28)	19.10
Participants who did not start IAD (N=8)	8.11

7. Secondary Outcome

Title	Median Time to Progression of HRPC in Participants Not Started on IAD Regimen
Description	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.
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	20
Median (95% Confidence Interval) [Months]	12.8

8. Secondary Outcome

Title	Median Survival Time
Description	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.
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

Participants who died while on study were used for analysis.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	4
All Participants (N=4)	18.94
Participants who started IAD (N=2)	24.44
Participants who did not start IAD (N=2)	12.76

9. Other Pre-specified Outcome

Title	Number of Participants Who Received IAD Regimen During the Study
Description	The data are reported as number of participants.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Data are of measurements collected from participants who started IAD.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	243
All participants	243 85.9%
Participants with no progression	210 74.2%
Participants with progression	33 11.7%

10. Other Pre-specified Outcome

Title	Number of Participants Who Continued to Take Leuprorelin in IAD Regimen by the End of the Study
Description	The data are reported as number of participants.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Data are of measurements collected from participants who started IAD.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	243
All participants	69 24.4%
Participants with no progression (N=210)	68 24%
Participants with progression (N=33)	1 0.4%

11. Primary Outcome

Title	Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen
Description	The data are reported as percentage of participants.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	283
Overall Study	31.4 11.1%
Cycle 1	15.2 5.4%
Cycle 2 (N=240)	14.6 5.2%
Cycle 3 (N=119)	62.2 22%
Cycle 4 (N=17)	64.7 22.9%
Cycle 5 (N=1)	0.0 0%

12. Secondary Outcome

Title	Mean Duration of Treatment-off Time in IAD Regimen
Description	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.
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

Data are of measurements collected from participants who started IAD.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	243
Mean (Standard Deviation) [Months]	7.12 (2.61)

13. Primary Outcome

Title	Number of Participants Who Switched to IAD Regimen by Visit
Description	The data are reported as number of participants.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	283
Visit 2 After One Year (N=257)	237 83.7%
Visit 3 After Two Years (N=225)	197 69.6%

14. Secondary Outcome

Title	Median Percentage of Time Off-treatment During 2 Years IAD Regimen
Description	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.
Time Frame	Baseline (enrollment), after 1 year, after 2 years, and 30 days from 2 year visit

Outcome Measure Data

Analysis Population Description

Data are of measurements collected from participants who started IAD.

Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
Measure Participants	243
Median (Full Range) [Percentage of time off-treatment]	33.45

Adverse Events

Time Frame	From signing of informed consent up to 24 months of observation of treatment period and 30 days of follow up period
Arm/Group Title	Advanced PCa
Arm/Group Description	Participants with advanced PCa
All Cause Mortality
	Advanced PCa
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Advanced PCa
	Affected / at Risk (%)	# Events
Total	13/283 (4.6%)
Cardiac disorders
CARDIAC DISORDER	1/283 (0.4%)
MYOCARDIAL INFARCTION	1/283 (0.4%)
General disorders
DISEASE PROGRESSION	7/283 (2.5%)
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	1/283 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	1/283 (0.4%)
RENAL CANCER	1/283 (0.4%)
Renal and urinary disorders
URINARY RETENTION	1/283 (0.4%)
Other (Not Including Serious) Adverse Events
	Advanced PCa
	Affected / at Risk (%)	# Events
Total	73/283 (25.8%)
Cardiac disorders
CARDIAC DISORDER	1/283 (0.4%)
MYOCARDIAL INFARCTION	1/283 (0.4%)
Gastrointestinal disorders
GASTRITIS	3/283 (1.1%)
PEPTIC ULCER	2/283 (0.7%)
GASTRIC ULCER	1/283 (0.4%)
General disorders
DISEASE PROGRESSION	13/283 (4.6%)
FATIGUE	5/283 (1.8%)
ASTHENIA	1/283 (0.4%)
OEDEMA	1/283 (0.4%)
Hepatobiliary disorders
CHOLECYSTITIS ACUTE	1/283 (0.4%)
Infections and infestations
NASOPHARYNGITIS	31/283 (11%)
BRONCHITIS	16/283 (5.7%)
PNEUMONIA	1/283 (0.4%)
Injury, poisoning and procedural complications
RIB FRACTURE	1/283 (0.4%)
Metabolism and nutrition disorders
DIABETES MELLITUS	3/283 (1.1%)
Musculoskeletal and connective tissue disorders
ARTHRITIS	1/283 (0.4%)
ARTHROPATHY	1/283 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	1/283 (0.4%)
RENAL CANCER	1/283 (0.4%)
Psychiatric disorders
DEPRESSION	1/283 (0.4%)
Renal and urinary disorders
URINARY RETENTION	1/283 (0.4%)
Reproductive system and breast disorders
GYNAECOMASTIA	6/283 (2.1%)
BREAST ENLARGEMENT	4/283 (1.4%)
ACQUIRED HYDROCELE	1/283 (0.4%)
ERECTILE DYSFUNCTION	1/283 (0.4%)
Respiratory, thoracic and mediastinal disorders
COUGH	3/283 (1.1%)
Skin and subcutaneous tissue disorders
DERMATITIS	5/283 (1.8%)
Vascular disorders
HOT FLUSH	12/283 (4.2%)
HYPERTENSION	2/283 (0.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.