A Study of Leuprolide to Treat Prostate Cancer

July 15, 2011 updated by: Abbott

A Phase 3, Multi-Center, Open-Label, Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Two 6-Month Leuprolide Formulations, in Subjects With Prostatic Adenocarcinoma

To assess the efficacy and safety of 2 new formulations of leuprolide acetate 45 mg 6-month depot, Formulation A or Formulation B, for the treatment of patients with prostate cancer. A formulation will be deemed successful if the percentage of subjects with suppression of testosterone to <= 50 ng/dL from Week 4 to Week 48 is not less than 87%, (the lower bound of the 2-sided 90% confidence interval), a protocol-specified criterion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A total of 300 male subjects were planned to be enrolled. Subjects were to receive a total of 2 intramuscular (IM) injections of the same formulation, either Formulation A or Formulation B, administered 24 weeks apart. The first 150 subjects were to receive Formulation A for both injections and the next 150 subjects were to receive Formulation B for both injections. The sponsor was to conduct an ongoing review of the primary endpoint data (suppression of testosterone <= 50 ng/dL) and planned to stop enrollment of Formulation A or Formulation B, or not to administer the second injection of Formulation A or Formulation B, if 15 or more subjects did not achieve testosterone suppression by Week 4 or failed to maintain testosterone suppression during the treatment period.

All analyses and summaries were to be conducted separately for subjects who received Formulation A or Formulation B.

This study was to be conducted at approximately 60-80 investigative sites. Subjects participated in the trial for approximately 14 months.

This trial was to include a Screening Period (up to 4 weeks), a 12-month Treatment Period (two 6-month treatment cycles), and a Follow-Up Period (30 days).

Study Type

Interventional

Enrollment (Actual)

310

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35209
        • Site Reference ID/Investigator# 8696
      • Homewood, Alabama, United States, 35209
        • Site Reference ID/Investigator# 8681
    • Alaska
      • Anchorage, Alaska, United States, 99508
        • Site Reference ID/Investigator# 8569
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Site Reference ID/Investigator# 9709
      • Sierra Vista, Arizona, United States, 85635
        • Site Reference ID/Investigator# 8662
      • Tucson, Arizona, United States, 85710
        • Site Reference ID/Investigator# 8656
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Site Reference ID/Investigator# 9705
    • California
      • Anaheim, California, United States, 92801
        • Site Reference ID/Investigator# 8691
      • Atherton, California, United States, 94027
        • Site Reference ID/Investigator# 8566
      • Fresno, California, United States, 93720
        • Site Reference ID/Investigator# 8686
      • Laguna Hills, California, United States, 92653
        • Site Reference ID/Investigator# 8698
      • Long Beach, California, United States, 90806
        • Site Reference ID/Investigator# 9703
      • Los Angeles, California, United States, 90015
        • Site Reference ID/Investigator# 8674
      • Tarzana, California, United States, 91356
        • Site Reference ID/Investigator# 8650
      • Torrance, California, United States, 90505
        • Site Reference ID/Investigator# 8699
    • Colorado
      • Denver, Colorado, United States, 80211
        • Site Reference ID/Investigator# 8668
      • Englewood, Colorado, United States, 80113
        • Site Reference ID/Investigator# 8646
    • Connecticut
      • Middlebury, Connecticut, United States, 06762
        • Site Reference ID/Investigator# 8652
      • New Britain, Connecticut, United States, 06052
        • Site Reference ID/Investigator# 8697
    • Florida
      • Aventura, Florida, United States, 33180
        • Site Reference ID/Investigator# 8655
      • Daytona Beach, Florida, United States, 32114
        • Site Reference ID/Investigator# 8648
      • New Smyrna Beach, Florida, United States, 32168
        • Site Reference ID/Investigator# 8660
      • Orange City, Florida, United States, 32763
        • Site Reference ID/Investigator# 8658
      • Orlando, Florida, United States, 32803
        • Site Reference ID/Investigator# 8664
      • Saint Augustine, Florida, United States, 32086
        • Site Reference ID/Investigator# 8651
      • St. Petersburg, Florida, United States, 33710
        • Site Reference ID/Investigator# 8661
      • Tallahassee, Florida, United States, 32308
        • Site Reference ID/Investigator# 8568
      • Wellington, Florida, United States, 33414
        • Site Reference ID/Investigator# 8679
      • West Palm Beach, Florida, United States, 33407
        • Site Reference ID/Investigator# 8562
    • Georgia
      • Roswell, Georgia, United States, 30076
        • Site Reference ID/Investigator# 8670
      • Thomasville, Georgia, United States, 31799
        • Site Reference ID/Investigator# 9708
    • Indiana
      • Fort Wayne, Indiana, United States, 46825
        • Site Reference ID/Investigator# 8693
      • Newburgh, Indiana, United States, 47630
        • Site Reference ID/Investigator# 8690
    • Kansas
      • Overland Park, Kansas, United States, 66211
        • Site Reference ID/Investigator# 8565
    • Maryland
      • Greenbelt, Maryland, United States, 20770
        • Site Reference ID/Investigator# 8676
    • Nevada
      • Las Vegas, Nevada, United States, 89148
        • Site Reference ID/Investigator# 8653
    • New Jersey
      • Lawrenceville, New Jersey, United States, 08648
        • Site Reference ID/Investigator# 8667
    • New York
      • Bronx, New York, United States, 10461
        • Site Reference ID/Investigator# 9702
      • New York, New York, United States, 10016
        • Site Reference ID/Investigator# 8665
      • Poughkeepsie, New York, United States, 12601
        • Site Reference ID/Investigator# 8657
    • North Carolina
      • Charlotte, North Carolina, United States, 28209
        • Site Reference ID/Investigator# 8680
      • Concord, North Carolina, United States, 28025
        • Site Reference ID/Investigator# 8673
      • Raleigh, North Carolina, United States, 27607
        • Site Reference ID/Investigator# 8666
      • Salisbury, North Carolina, United States, 28144
        • Site Reference ID/Investigator# 8570
      • Winston-Salem, North Carolina, United States, 27103
        • Site Reference ID/Investigator# 8644
    • Ohio
      • Cincinnati, Ohio, United States, 45212
        • Site Reference ID/Investigator# 8663
      • Columbus, Ohio, United States, 43220
        • Site Reference ID/Investigator# 8567
    • Oklahoma
      • Bethany, Oklahoma, United States, 73008
        • Site Reference ID/Investigator# 8678
    • Pennsylvania
      • Bala Cynwyd, Pennsylvania, United States, 19004
        • Site Reference ID/Investigator# 8563
      • Lancaster, Pennsylvania, United States, 17604-3200
        • Site Reference ID/Investigator# 8692
    • South Carolina
      • Myrtle Beach, South Carolina, United States, 29572
        • Site Reference ID/Investigator# 8689
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Site Reference ID/Investigator# 8643
      • Germantown, Tennessee, United States, 38138
        • Site Reference ID/Investigator# 8695
      • Memphis, Tennessee, United States, 38119
        • Site Reference ID/Investigator# 8685
      • Nashville, Tennessee, United States, 37209
        • Site Reference ID/Investigator# 8564
      • Nashville, Tennessee, United States, 37232-2765
        • Site Reference ID/Investigator# 8645
    • Texas
      • Dallas, Texas, United States, 75231
        • Site Reference ID/Investigator# 8641
      • Houston, Texas, United States, 77024
        • Site Reference ID/Investigator# 8675
      • San Antonio, Texas, United States, 78229
        • Site Reference ID/Investigator# 8684
      • Tyler, Texas, United States, 75701
        • Site Reference ID/Investigator# 8649
    • Utah
      • Salt Lake City, Utah, United States, 84107
        • Site Reference ID/Investigator# 8683
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • Site Reference ID/Investigator# 8672
      • Richmond, Virginia, United States, 23235
        • Site Reference ID/Investigator# 8669

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Voluntarily sign an IRB-approved informed consent form and any required privacy statement/authorization form.
  • Pre-trial serum testosterone level >150 ng/dL.

  • Histologically-confirmed prostatic adenocarcinoma in Jewett Clinical Stage A2, B, C or D and TNM* classification cT1b-4, N: any, M: any.

    *Tumor/Nodes/Metastases

  • Subjects with a rising PSA following radical prostatectomy defined as an increase of 0.2 ng/mL from the previous test on two consecutive testings or rising PSA following prostate irradiation using Phoenix Definition of a rise of greater than or equal to 2.0 ng/mL above the nadir.
  • Prostate cancer and general clinical status is sufficient to warrant at least 48 weeks of continuous androgen deprivation treatment, without concomitant antiandrogen treatment.
  • Eastern Cooperative Oncology Group (ECOG) Performance status grades 0,1,or 2 at the time of pre-trial screening.
  • Life expectancy of at least 18 months.
  • Subjects with serum creatinine ≤1.9 mg/dL, bilirubin ≤2.0 mg/dL (unless Gilbert's syndrome with normal AST, ALT); AST and ALT ≤2.5 times the upper limit of normal.

Exclusion Criteria:

  • Requires additional treatment including radical prostatectomy, radiotherapy or cryotherapy of local disease.
  • Historical, clinical, or radiographic evidence of central nervous system metastases, including spinal cord metastasis.
  • Clinical evidence of urinary tract obstruction.
  • History of bilateral orchiectomy, adrenalectomy, or hypophysectomy.
  • History of clinical hypogonadism.
  • Current malignancy or history of malignancy except for prostate cancer or basal or squamous cell carcinoma of the skin.
  • Clinical or laboratory evidence of any severe underlying disease state (excluding prostate cancer) that would place subjects in additional jeopardy by participating in this trial.
  • Hypersensitivity to leuprolide, polylactic acid, or any excipient of the drug.
  • Incomplete recovery from the effects of any major surgery.
  • History of receiving of the following prostate cancer therapies within 8 weeks prior to the Screening Visit: chemotherapy, immunotherapy, antiandrogen, radiation therapy, cryotherapy, strontium, or biological response modifiers.
  • History of prostatic surgery within 4 weeks prior to the Screening Visit.
  • Received hormonal therapy, including GnRH analogs (less than or equal to 6 month depot administration), estrogen, Megace and phytotherapy, within 32 weeks prior to the Screening Visit and during the trial.
  • Alternative medical therapies which have an estrogenic, androgenic, or antiandrogenic effect (including phyto-estrogens and phyto-androgens) within 12 weeks prior to the Screening Visit and during the trial.
  • Requires the chronic use of systemic corticosteroids and anticonvulsants that may affect bone loss such as carbamazepine, phenobarbital, phenytoin, valproic acid or primidone.
  • May require antiandrogen, immuno-, or surgical therapy for prostate cancer during the trial.
  • History of alcoholism or consumes >14 alcoholic beverages per week or illicit drug abuse within 12 months prior to screening.
  • Received therapy with a GnRH analog (1 year implant) within 60 weeks prior to the Screening Visit.
  • Received therapy with finasteride or ketoconazole within 1 week prior to the Screening Visit; dutasteride within 25 weeks prior to the Screening Visit.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Leuprolide acetate - Formulation A
Leuprolide acetate 45 mg, 6-month depot
Drug: Leuprolide acetate - Formulation A
Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation A, 45 mg 6 month depot, 24 weeks apart.
Other Names:
  • Lupron
  • leuprorelin
  • gonadotropin hormone-releasing hormone (GnRH)
  • luteinizing hormone-releasing hormone (LHRH)
EXPERIMENTAL: Leuprolide acetate - Formulation B
Leuprolide acetate, 45 mg, 6-month depot
Drug: Leuprolide acetate - Formulation B
Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation B, 45 mg 6 month depot, 24 weeks apart.
Other Names:
  • Lupron
  • leuprorelin
  • gonadotropin hormone-releasing hormone (GnRH)
  • luteinizing hormone-releasing hormone (LHRH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: Intent-to-treat (ITT) Population for the Primary Endpoint.
Time Frame: Week 4 to Week 48
The percentage of subjects with testosterone suppression (<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Week 4 to Week 48
Adjusted Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation A: ITT Population for the Primary Endpoint Adjusted
Time Frame: Week 4 to Week 48
The adjusted percentage of subjects with testosterone suppression (<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. The primary efficacy analysis was adjusted to censor subjects who received an anti-androgen at the last testosterone measurement before use of the anti-androgen. One additional subject was censored because of a laboratory error, at the last measurement before the error. The adjusted 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Week 4 to Week 48
Percentage of Subjects With Suppression of Serum Testosterone (<=50 ng/dL) From Week 4 to Week 48 for Formulation B: ITT Population for the Primary Endpoint Preplanned
Time Frame: Week 4 to Week 48
The percentage of subjects with testosterone suppression (<= 50 ng/dL) from Week 4 to Week 48 was calculated by the Kaplan-Meier method for right-censored observations. Subjects who failed testosterone suppression were considered failures on the first day of a testosterone measurement (>50 ng/dL). Subjects who prematurely discontinued without escaping and those who were successfully suppressed through Week 48 were censored at their last measured testosterone value (Day 337 to Day 340 at Week 48). The 90% 2-sided confidence interval was calculated from Kaplan-Meier estimates.
Week 4 to Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population
Time Frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Baseline was the last measurement before the first dose of Formulation A. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population
Time Frame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Baseline was the last measurement before the first dose of Formulation B. The mean +/- standard error was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population
Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 hours [h], 4 h, 8 h, 1 day [d], 2 d, 3-10 d, and 11-17 d postdose)
The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Week 24 before the second injection until 2 weeks after Week 24 (2 hours [h], 4 h, 8 h, 1 day [d], 2 d, 3-10 d, and 11-17 d postdose)
Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population
Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
The acute-on-chronic effect is an agonistic stimulation of serum testosterone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population
Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation A. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population
Time Frame: Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
The acute-on-chronic effect is an agonistic stimulation of luteinizing hormone after the second depot injection of Formulation B. The mean +/- standard error changes were measured to assess this effect from just before to 2 weeks after the second injection.
Week 24 before the second injection until 2 weeks after Week 24 (2 h, 4 h, 8 h, 1 d, 2 d, 3-10 d, and 11-17 d postdose)
Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population
Time Frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
PSA levels were measured at baseline and each treatment visit for Formulation A. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population
Time Frame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
PSA levels were measured at baseline and each treatment visit for Formulation B. The mean (+/- standard error) was calculated at each visit. The final visit occurred at Week 48 unless the subject prematurely discontinued the study.
Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abbott

Investigators

  • Study Director: Kristof Chwalisz, MD, PhD, Abbott

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2008

Primary Completion (ACTUAL)

August 1, 2009

Study Completion (ACTUAL)

September 1, 2009

Study Registration Dates

First Submitted

February 20, 2008

First Submitted That Met QC Criteria

February 20, 2008

First Posted (ESTIMATE)

February 29, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

July 19, 2011

Last Update Submitted That Met QC Criteria

July 15, 2011

Last Verified

July 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L-PC07-169

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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