Trial Outcomes & Findings for A Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Participants With a Rising Prostate Specific Antigen (PSA) (NCT NCT00514917)

Last Updated: 2013-11-04

Results Overview

PFS was the time from randomization to the date of first documented prostate specific antigen (PSA) progression, or radiographic progression, or death due to prostate cancer in the absence of previous documentation of disease progression, whichever occurred first. PSA progression was determined as: a) During treatment period: a 50 percent (%) increase from baseline, which was confirmed by a second value; b) During follow-up: detectable PSA (defined as PSA greater than or equal to 0.05 nanogram per millimeter \[ng/mL\]), which was confirmed by consecutive observation (not less than 2 weeks apart). Median PFS was estimated using the Kaplan-Meier method.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

413 participants

Primary outcome timeframe

Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60

Results posted on

2013-11-04

Participant Flow

Participants were enrolled from 53 sites in North America (the United States of America and Canada) and Europe. Study was terminated after all participants had completed treatment with docetaxel, but before all participants had completed 18 months follow-up. The termination was not due to any safety or efficacy concerns.

Participant milestones

Participant milestones
Measure	Docetaxel+Leuprolide+Bicalutamide Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Overall Study STARTED	207	206
Overall Study Treated	196	204
Overall Study Completed Study Treatment	170	182
Overall Study Testosterone-Specific Evaluable	122	124
Overall Study COMPLETED	81	91
Overall Study NOT COMPLETED	126	115

Reasons for withdrawal

Reasons for withdrawal
Measure	Docetaxel+Leuprolide+Bicalutamide Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Overall Study Death	4	10
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	4	3
Overall Study Withdrawal by Subject	18	16
Overall Study Discontinued due to study closure	88	81
Overall Study Undefined	11	5

Baseline Characteristics

A Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Participants With a Rising Prostate Specific Antigen (PSA)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Docetaxel+Leuprolide+Bicalutamide n=196 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=204 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Total n=400 Participants Total of all reporting groups
Age Continuous	65.2 years STANDARD_DEVIATION 6.97 • n=5 Participants	64.0 years STANDARD_DEVIATION 6.97 • n=7 Participants	64.6 years STANDARD_DEVIATION 6.99 • n=5 Participants
Age, Customized Less Than (<) 65 Years	86 participants 43.9 • n=5 Participants	104 participants 51.0 • n=7 Participants	190 participants n=5 Participants
Age, Customized Greater Than or Equal to (>=) 65 to < 75 Years	95 participants 48.5 • n=5 Participants	89 participants 43.6 • n=7 Participants	184 participants n=5 Participants
Age, Customized >= 75 Years	15 participants 7.7 • n=5 Participants	11 participants 5.4 • n=7 Participants	26 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	196 Participants n=5 Participants	204 Participants n=7 Participants	400 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/White	175 participants n=5 Participants	184 participants n=7 Participants	359 participants n=5 Participants
Race/Ethnicity, Customized Black	16 participants n=5 Participants	13 participants n=7 Participants	29 participants n=5 Participants
Race/Ethnicity, Customized Asian/Oriental	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Others	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Body Surface Area (BSA)	2.05 square meter (m^2) STANDARD_DEVIATION 0.176 • n=5 Participants	2.08 square meter (m^2) STANDARD_DEVIATION 0.194 • n=7 Participants	2.06 square meter (m^2) STANDARD_DEVIATION 0.186 • n=5 Participants
Prior Radiation Therapy	63 participants n=5 Participants	75 participants n=7 Participants	138 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60

Population: ITT population included all participants who were randomized, with study drug assignment designated according to randomization, regardless of whether participants received any study drug or a different drug from that to which they were randomized.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=207 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=206 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Median Progression-Free Survival (PFS) in Intent-to-treat (ITT) Population	25.4 months Interval 23.8 to 27.8	23.3 months Interval 22.6 to 25.1

PRIMARY outcome

Timeframe: Month 36

Population: ITT population.

PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=207 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=206 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Progression-Free Survival (PFS) Rate at Month 36 in ITT Population	15.5 percent chance of being progression-free Interval 9.1 to 23.3	8.6 percent chance of being progression-free Interval 3.8 to 16.0

PRIMARY outcome

Timeframe: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60

Population: Testosterone-specific evaluable population included all participants who recovered testosterone to non-castrate levels (50 ng/mL) following the completion of treatment of leuprolide with at least 1 follow-up PSA assessment.

PFS was the time from randomization to the date of first documented PSA progression, or radiographic progression, or death due to prostate cancer in the absence of previous documentation of disease progression, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=122 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=124 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Median Progression-Free Survival (PFS) in Testosterone Specific Evaluable Population	25.7 months Interval 25.1 to 28.1	24.7 months Interval 22.8 to 25.3

PRIMARY outcome

Timeframe: Month 36

Population: Testosterone-specific evaluable population included all participants who recovered testosterone to non-castrate levels (50 ng/mL) following completion of treatment of leuprolide with at least 1 follow-up PSA assessment.

PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=122 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=124 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable Population	15.8 percent chance of being progression-free Interval 9.0 to 24.3	9.1 percent chance of being progression-free Interval 4.0 to 16.7

SECONDARY outcome

Timeframe: Randomization until death due to any cause, assessed up to Month 60

Population: ITT population.

The OS was the time interval from the date of randomization to the date of death due to any cause. OS was to be analyzed using the Kaplan-Meier method. However, the analysis was not performed due to insufficient number of events. Reported is the number of participants who died from any cause.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=207 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=206 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Overall Survival (OS): Number of Participants Who Died (All Cause)	4 participants	11 participants

SECONDARY outcome

Timeframe: Randomization until death due to prostate cancer, assessed up to Month 60

Population: ITT population.

The cancer-specific survival was the time from the date of randomization to the date of death due to prostate cancer. Cancer-specific survival was to be analyzed using the Kaplan-Meier method. However, the analysis was not performed due to insufficient number of events. Reported is the number of participants who died from prostate cancer.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=207 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=206 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific)	2 participants	3 participants

SECONDARY outcome

Timeframe: Baseline, EOT (up to Month 18)

Population: ITT population. Here "N" (number of participants analyzed) signifies participants who were evaluable for this measure and "n" signifies participants evaluable at each time-point for each treatment arm, respectively.

FACT-P is a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life with fewer symptoms. A score of 156 represents the best outcome.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=206 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=205 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT) Baseline (n=206, 205)	121.4 units on a scale Standard Deviation 18.32	119.6 units on a scale Standard Deviation 17.95
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT) Change at EOT (n=186, 184)	-4.9 units on a scale Standard Deviation 13.55	-3.4 units on a scale Standard Deviation 14.78

SECONDARY outcome

Timeframe: Baseline, EOT (up to Month 18)

Physical well-being, functional well-being, and prostate cancer concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=206 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=206 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT Baseline (n=206, 206)	82.1 units on a scale Standard Deviation 12.58	80.4 units on a scale Standard Deviation 12.52
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT Change at EOT (n=187, 187)	-5.4 units on a scale Standard Deviation 10.19	-3.1 units on a scale Standard Deviation 11.83

SECONDARY outcome

Timeframe: Baseline, EOT (up to Month 18)

MAF scale consists of 16-items to measure 4 dimensions of fatigue during past week: severity (Item 1-2), distress (Item 3), degree of interference in activities of daily living (Item 4-14), and timing (Item 15-16). Item 1-14 are scored on a numeric rating scale from 1 to 10, where higher score indicate more severity/distress/interference. Item 15-16 had multiple choice responses (4 responses each). Scale Index was calculated using Item 1-15, in following steps: 1) Item 15 score converted to 1-10 scale by multiplying the score with 2.5; 2) Average score was calculated from Item 4-14; 3) Finally scale index was calculated by adding Items 1, 2, 3 scores with average score from step 2 and converted score of Item 15 from step 1. Total MAF scale index score ranges 1 (no fatigue) to 50 (severe fatigue).

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=168 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=171 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT Baseline (n=168, 171)	16.4 units on a scale Standard Deviation 7.33	16.6 units on a scale Standard Deviation 7.93
Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT Change at EOT (n=127, 144)	4.0 units on a scale Standard Deviation 8.93	2.6 units on a scale Standard Deviation 8.60

SECONDARY outcome

Timeframe: Baseline, EOT (up to Month 18)

EF-IIEF is a 6-item erectile function domain of IIEF. It consists of Question 1, 2, 3, 4, 5, and 15 of IIEF questionnaire. 5 questions are scored from 0 (no activity) to 5 (very high activity) and 1 question is scored from 1 (very low activity) to 5 (very high activity). Total EF-IIEF score ranges from 1 to 30, where higher score indicates high activity.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=201 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=205 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT Baseline (n=201, 205)	6.4 units on a scale Standard Deviation 8.30	6.8 units on a scale Standard Deviation 8.25
Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT Change at EOT (n=180, 186)	-3.1 units on a scale Standard Deviation 7.15	-3.3 units on a scale Standard Deviation 7.11

OTHER_PRE_SPECIFIED outcome

Timeframe: From first administration of study treatment until 30 days after the last administration of study treatment

Population: Safety population included all randomized participants who received at least part of one dose of any of the study drugs.

TEAE: any adverse event (AE) that occurred or worsened during the on-treatment period, which was the period from first administration of study treatment until 30 days after last administration of study treatment. AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AE: an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly, or medically important. Drug-related AEs were any untoward medical occurrences attributed to study drug in a participant who received study drug. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 Grade 3 (severe) and Grade 4 (life threatening/disabling) TEAEs were also reported.

Outcome measures

Outcome measures
Measure	Docetaxel+Leuprolide+Bicalutamide n=196 Participants Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles (3 week cycle) along with leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.	Leuprolide+Bicalutamide n=204 Participants Participants received leuprolide 22.5 mg injection subcutaneously every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE	188 participants	163 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any Serious AE	49 participants	20 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE Resulting in Death	0 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE Leading to any Treatment Discontinuation	35 participants	1 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any Grade 3-4 TEAE	94 participants	22 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Docetaxel Related TEAE	183 participants	NA participants Participants in this treatment arm did not receive docetaxel.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leuprolide Related TEAE	109 participants	136 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Bicalutamide Related TEAE	52 participants	74 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any Treatment Related TEAE	184 participants	136 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any Grade 3-4 Serious TEAE	43 participants	14 participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE Leading to Interruption of any Treatment	77 participants	1 participants

Adverse Events

Docetaxel+Leuprolide+Bicalutamide

Serious events: 49 serious events

Other events: 185 other events

Deaths: 0 deaths

Leuprolide+Bicalutamide

Serious events: 20 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The investigator shall provide the Steering Committee a copy of any manuscript, abstract or oral communication derived from the study for review and comment at least 30 days in advance of any submission. The Sponsor's representatives shall have the right to review and/or delay any publication or presentation to prevent disclosure of Sponsor's confidential information and preserve intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER