Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Reproductive Control Agents

Androgens

Docetaxel

Leuprolide

Bicalutamide

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Hormonal

Androgen Antagonists

Hormones

Hormone Antagonists

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.

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.

75 mg/m\^2 intravenous infusion over 1 hour every 3 weeks up to 10 cycles.

22.5 mg injection subcutaneously every 12 weeks up to 18 months.

50 mg tablet orally once daily for first 4 weeks of treatment.

Barrett Childs, MD

The primary objective was to evaluate and compare the efficacy of androgen deprivation with or without docetaxel as determined by the median progression free survival (PFS) over the period of 18-month therapy and at least 18-month follow-up.

The secondary objectives were:

* To assess cancer specific survival;
* To compare overall survival between the 2 treatment groups;
* To evaluate patient-reported outcomes including quality of life, fatigue, and sexual functioning as measured by 3 different assessments.

The duration of the study per participant was to be at least 36 months, of which the treatment period was 18 months for all participants, followed by at least 18 months follow-up period.

Participants received study treatment for up to 18 months from the time of study therapy initiation or less if one of the following occurred: disease progression, unacceptable toxicity, death, participant refusal or treatment delay beyond the time frame that is permitted for each treatment.

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

A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Subjects With a Rising PSA Following Definitive Local Therapy

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

Sanofi

The analysis was performed on safety population, defined as all randomized participants who received at least part of one dose of any of the study drugs, and included all TEAEs that developed or worsened from first administration of study treatment until 30 days after last administration of study treatment.

Docetaxel+Leuprolide+Bicalutamide

Leuprolide+Bicalutamide

Total

Age Continuous

Less Than (<) 65 Years

Greater Than or Equal to (>=) 65 to < 75 Years

>= 75 Years

Age, Customized

Sex: Female, Male

Caucasian/White

Black

Asian/Oriental

Others

Race/Ethnicity, Customized

BSA was calculated using the Dubois and Dubois formula: BSA (in square meter) = (weight\^0.425\* height\^0.725)\*0.007184; where weight is in kilogram (kg) and height is in centimeter (cm). Here "N" (number of participants analyzed) = 192, 198 for each treatment arm, respectively.

Body Surface Area (BSA)

Prior Radiation Therapy

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

Trial Transparency Team

Null hypothesis: No difference between new treatment combination (Docetaxel+Leuprolide+Bicalutamide) and conventional treatment (Leuprolide+Bicalutamide).

The study was sized to have 90% power to detect a difference between treatment arms at a 2-sided 0.05 significance level with 186 events and anticipating 10% non-evaluable participants.

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.

Median Progression-Free Survival (PFS) in Intent-to-treat (ITT) Population

Participants received docetaxel 75 milligram per square meter (mg/m\^2) intravenous infusion over 1 hour every 3 weeks up to 10 cycles along with leuprolide 22.5 mg/m\^2subcutaneous injection for every 12 weeks up to 18 months and bicalutamide 50 mg tablet orally once daily for first 4 weeks of treatment.

Participants received leuprolide 22.5 mg/m\^2 subcutaneous injection for 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

Overall Survival (OS): Number of Participants Who Died (All Cause)

Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific)

Baseline (n=206, 205)

Change at EOT (n=186, 184)

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.

Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT)

Baseline (n=206, 206)

Change at EOT (n=187, 187)

Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT

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.

Median Progression-Free Survival (PFS) in Testosterone Specific Evaluable Population

Baseline (n=168, 171)

Change at EOT (n=127, 144)

Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT

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.

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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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