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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01320735

Enrollment

300

Registered

2011-03-22

Start date

2011-02-28

Completion date

2014-05-31

Last updated

2015-07-08

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

Conditions

Prostate Cancer

Keywords

Lucrin Depot, intermittent adjuvant regimen, advanced prostate cancer, Leuprorelin

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)

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.

Interventions

None listed

Study design

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

MALE

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Histologically confirmed advanced PCa meeting the following criteria: 1. Any Tumor, Node 1, Metastasis 0 2. Any Tumor, Node 0, Metastasis 1 \[according to Tumor Node Metastasis classification 2009\] 2. Participants planned for administration of leuprorelin 3. World Health Organization status 0-1 4. Life expectancy at least 2 years

Exclusion criteria

1. Contraindications to administration of leuprorelin: 1. Hypersensitivity to Leuprorelin similar products of protein origin or any of the excipients in drug product composition 2. Surgical castration 2. Hormone-refractory PCa 3. Presence of another malignant tumor (except skin cancer) 4. Previous administration of hormone therapy with gonadotropin-releasing hormone agonists or antiandrogens 5. Previous administration of radiotherapy or chemotherapy course within 1 month 6. Testosterone level less than or equal to 50 ng/dl (less than or equal to 1.7 mmol/l) at time of inclusion 7. Extremely high level of PSA (greater than or equal to 1000 ng/ml) 8. Other severe diseases in stage of decompensation 9. Other contraindications, that make the participant's participation impossible (by investigator judgment) 10. Previous enrollment in the present program

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen	24 months	The data are reported as percentage of participants.
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.
Number of Participants Who Switched to IAD Regimen by Visit	24 months	The data are reported as number of participants.
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.
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.

Secondary

Measure	Time frame	Description
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.
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.
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.
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).
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.
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.

Other

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

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
Advanced PCa Participants with advanced PCa	283
Total	283

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative Reason	6
Overall Study	Adverse Event	3
Overall Study	Investigator Unable to be Contacted	17
Overall Study	Lost to Follow-up	13
Overall Study	No Decrease of Prostate Specific Antigen	7
Overall Study	Other	1
Overall Study	Progression/Hormone-Refractory Pca	55
Overall Study	Protocol Violation	1
Overall Study	Withdrawal by Subject	3

Baseline characteristics

Characteristic	Advanced PCa
Age, Continuous	65.4 Years STANDARD_DEVIATION 6.3
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	283 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	73 / 283
serious Total, serious adverse events	13 / 283

Outcome results

Primary

Mean Duration of Each Leuprorelin Cycle

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

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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	All Participants: Cycle 1 (N=282)	7.63 Months	Standard Deviation 1.73
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	All Participants: Cycle 2 (N=238)	5.60 Months	Standard Deviation 2.21
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	All Participants: Cycle 3 (N=61)	4.64 Months	Standard Deviation 1.63
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	All Participants: Cycle 4 (N=7)	3.44 Months	Standard Deviation 1.09
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	All Participants: Cycle 5 (N=1)	3.30 Months	—
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with No Progression: Cycle 1 (N=226)	7.68 Months	Standard Deviation 1.49
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with No Progression: Cycle 2 (206)	5.70 Months	Standard Deviation 2.08
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with No Progression: Cycle 3 (N=52)	4.72 Months	Standard Deviation 1.55
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with No Progression: Cycle 4 (N=7)	3.44 Months	Standard Deviation 1.09
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with No Progression: Cycle 5 (N=1)	3.30 Months	—
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with Progression: Cycle 1 (N=56)	7.43 Months	Standard Deviation 2.49
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with Progression: Cycle 2 (N=32)	4.96 Months	Standard Deviation 2.84
Advanced PCa	Mean Duration of Each Leuprorelin Cycle	Participants with Progression: Cycle 3 (N=9)	4.19 Months	Standard Deviation 2.08

Primary

Mean Duration of Leuprorelin Exposure

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

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.

Arm	Measure	Group	Value (MEAN)	Dispersion
Advanced PCa	Mean Duration of Leuprorelin Exposure	All participants	19.74 Months	Standard Deviation 6.39
Advanced PCa	Mean Duration of Leuprorelin Exposure	Participants with no progression (N=227)	21.25 Months	Standard Deviation 5.31
Advanced PCa	Mean Duration of Leuprorelin Exposure	Participants with progression (N=56)	13.62 Months	Standard Deviation 6.79

Primary

Median Number of Leuprorelin Cycles

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

Time frame: 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.

Arm	Measure	Value (MEDIAN)
Advanced PCa	Median Number of Leuprorelin Cycles	2 Cycles

Primary

Number of Participants Who Switched to IAD Regimen by Visit

The data are reported as number of participants.

Time frame: 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.

Arm	Measure	Group	Value (NUMBER)
Advanced PCa	Number of Participants Who Switched to IAD Regimen by Visit	Visit 2 After One Year (N=257)	237 Participants
Advanced PCa	Number of Participants Who Switched to IAD Regimen by Visit	Visit 3 After Two Years (N=225)	197 Participants

Primary

Percentage of Participants Who Discontinued From Leuprorelin Administration of IAD Regimen

The data are reported as percentage of participants.

Time frame: 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.

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

Secondary

Mean Duration of Treatment-off Time in IAD Regimen

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.