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

NCT00514917 | Terminated Phase 3 Results DMC

• 2 other identifiers: XRP6976J_35032007-000323-17
• Study Type: interventional
• Target: 413
• Locations: 9 countries
• Sites: 9

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.

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (4)

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

  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.

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

• Progression-Free Survival (PFS) Rate at Month 36 in 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.

  Month 36

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

  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.

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

• Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable 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.

  Month 36

Secondary Outcomes (6)

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

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

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

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

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

  Baseline, EOT (up to Month 18)

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

  Baseline, EOT (up to Month 18)

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

  Baseline, EOT (up to Month 18)

Other Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

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

Study Arms (2)

Docetaxel+Leuprolide+Bicalutamide

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Leuprolide; Drug: Bicalutamide

Leuprolide+Bicalutamide

ACTIVE COMPARATOR

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.

Drug: Leuprolide; Drug: Bicalutamide

Interventions

Docetaxel DRUG

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

Also known as: TAXOTERE®, XRP6976

Docetaxel+Leuprolide+Bicalutamide

Leuprolide DRUG

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

Also known as: Eligard®

Docetaxel+Leuprolide+Bicalutamide; Leuprolide+Bicalutamide

Bicalutamide DRUG

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

Docetaxel+Leuprolide+Bicalutamide; Leuprolide+Bicalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (9)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Sanofi-Aventis Administrative Office

Diegem, Belgium

Location

Sanofi-Aventis Administrative Office

Laval, Canada

Location

Sanofi-Aventis Administrative Office

Prague, Czechia

Location

Sanofi-Aventis Administrative Office

Frankfurt, Germany

Location

Sanofi-Aventis Administrative Office

Vilnius, Lithuania

Location

Sanofi-Aventis Administrative Office

Warsaw, Poland

Location

Sanofi-Aventis Administrative Office

Bratislava, Slovakia

Location

Sanofi-Aventis Administrative Office

Barcelona, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel; Leuprolide; luprolide acetate gel depot; bicalutamide

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-Us@sanofi.com

Study Officials

• Barrett Childs, MD

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2007
• First Posted: August 10, 2007
• Study Start: July 1, 2007
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 4, 2013
• Results First Posted: November 4, 2013

Record last verified: 2013-08

Locations

BE (1); CZ (1); DE (1); US (1); SL (1); ES (1); CA (1); LI (1); PL (1)