Clinical trial NCT00514917: A Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Participants With a Rising Prostate Specific Antigen (PSA)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Prostatic Neoplasms
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2007-08-10
Enrollment: 413
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of prostate adenocarcinoma pathologically confirmed
* History of radical prostatectomy (pre-operative radiation therapy to the prostate or pelvis or salvage radiation after radical prostatectomy was allowed)
* Demonstration of biochemical progression of disease based on prostate specific antigen (PSA) doubling time. The minimum PSA value for eligibility was greater than or equal to (\>=) 1. PSA doubling time over three values must be equal to (=) 9 months with a minimum of 3 weeks between assessments
* Serum testosterone \>=100 nanogram per deciliter (ng/dL)
* Karnofsky performance status (KPS) \>=70 percent (%)
* Adequate organ function as defined by the following laboratory criteria:

  * White blood cells \>=3500 per cubic millimeter (mm\^3)
  * Absolute neutrophil count (ANC) \>=1500 per mm\^3
  * Platelet count \>=100,000 per mm\^3
  * Hemoglobin \>= 10.0 gram per deciliter (g/dL)
  * Total Bilirubin less than or equal to (\<=) upper limit of normal (ULN) unless due to Gilbert's disease
  * Creatinine l \<= 1.5 milligram per deciliter (mg/dL) or creatinine clearance \>=60 cubic centimeters per minute
  * Aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase within pre-defined ranges
* Previous hormonal therapy was allowed provided that the total duration of therapy did not exceed 6 months
* Man of childbearing potential who was willing to consent to use effective contraception while on treatment and for at least 3 months thereafter
* Participant who was willing and was able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria:

* Clinically significant cardiac disease (New York Heart Association Class III/IV), or severe debilitating pulmonary disease
* Uncontrolled serious active infection
* Anticipated duration of life \< 2 years
* Less than 5-year history of successful treatment for other cancers or concurrent active nonprostate cancer other than nonmelanoma dermatologic tumor
* Peripheral neuropathy \>=Grade 2
* History of hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80, leuprolide, or bicalutamide
* Prior chemotherapy within the past 10 years (except non-taxane based chemotherapy for treatment of other cancers); concurrent treatment on another clinical trial or with any other cancer therapy including chemotherapy, immunotherapy, radiotherapy (except salvage radiation therapy), chemoembolization therapy, cryotherapy
* Other severe acute or chronic medical conditions including psychiatric disease, or significant laboratory abnormality requiring further investigation that may cause undue risk for the participant's safety, delay or prohibit protocol participation, or interfere with the interpretation of study results, and in the judgment of the investigator would make the participant inappropriate for entry into this study
* Radiographic findings suspicious for metastatic disease in the treating physician's clinical judgment. Participant who had radiographically suspicious pelvic lymph nodes prior to radial prostatectomy, but who, at the time of enrollment did not have suspicious adenopathy was eligible. Participant was eligible even if he/she had tumor-containing pelvic adenopathy at the time of surgery as long as at the time of enrollment there was no radiographically evident nodal disease in the clinician's opinion
* Participant was the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
* Participant unlikely to comply with protocol or research tests, for example, uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study
* Participant who participated in another clinical study/received investigational product within 30 days of screening

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Median Progression-Free Survival (PFS) in Intent-to-treat (ITT) Population
timeFrame: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60
measure: Progression-Free Survival (PFS) Rate at Month 36 in ITT Population
timeFrame: Month 36
measure: Median Progression-Free Survival (PFS) in Testosterone Specific Evaluable Population
timeFrame: Randomization until PSA progression or radiographic progression or death due to prostate cancer, assessed up to Month 60
measure: Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable Population
timeFrame: Month 36
Secondary outcomes:
measure: Overall Survival (OS): Number of Participants Who Died (All Cause)
timeFrame: Randomization until death due to any cause, assessed up to Month 60
measure: Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific)
timeFrame: Randomization until death due to prostate cancer, assessed up to Month 60
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT)
timeFrame: Baseline, EOT (up to Month 18)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT
timeFrame: Baseline, EOT (up to Month 18)
measure: Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT
timeFrame: Baseline, EOT (up to Month 18)
measure: Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT
timeFrame: Baseline, EOT (up to Month 18)
Other outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From first administration of study treatment until 30 days after the last administration of study treatment
Locations:
city: Bridgewater
country: United States
facility: Sanofi-Aventis Administrative Office
state: New Jersey
city: Diegem
country: Belgium
facility: Sanofi-Aventis Administrative Office
city: Laval
country: Canada
facility: Sanofi-Aventis Administrative Office
city: Praha
country: Czech Republic
facility: Sanofi-Aventis Administrative Office
city: Frankfurt
country: Germany
facility: Sanofi-Aventis Administrative Office
city: Vilnius
country: Lithuania
facility: Sanofi-Aventis Administrative Office
city: Warsaw
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Bratislava
country: Slovakia
facility: Sanofi-Aventis Administrative Office
city: Barcelona
country: Spain
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Barrett Childs, MD
role: STUDY_DIRECTOR
References: