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

Completed

• Conditions: Prostate Cancer

• Registration Number: NCT01320735
• Lead Sponsor: AbbVie (prior sponsor, Abbott)

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.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-02-14
• Study First Submitted QC: 2011-03-21
• Study First Posted: 2011-03-22
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Results First Submitted: 2015-05-19
• Status Verified: 2015-06
• Results First Submitted QC: 2015-06-11
• Last Update Submitted: 2015-06-11
• Results First Posted: 2015-07-08
• Last Update Posted: 2015-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 300

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.
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.