AzTrials
AzTrials

Prostate CancerPhase 3NCT01415960

Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer

A Phase 3 study testing Leuprolide acetate 22.5 mg depot, GP-Pharm SA in people with Prostate Cancer, run by GP-Pharm at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Some patients with prostate cancer benefit from androgen deprivation therapy which reduces levels of testosterone. Leuprolide is a synthetic Luteinizing hormone releasing hormone (LHRH) analogue which upon administration can decrease testosterone levels to ≤0.5 ng/mL. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
Leuprolide acetate 22.5 mg depot, GP-Pharm SA
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
163 participants
Where
25 sitesUnited States
Study dates
Sep 2011to Nov 2013
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Males ≥18 years of age
  • Patients with histologically documented prostate carcinoma who might benefit from medical androgen deprivation therapy.
  • Life expectancy of at least 1 year.
  • WHO/ECOG performance status of 0, 1, or 2.
  • Adequate renal function at Screening as defined by serum creatinine ≤1.6 times the upper limit of normal (ULN) for the clinical laboratory.
  • Adequate and stable hepatic function as defined by bilirubin ≤1.5 times the ULN and transaminases (i.e., aspartate aminotransferase, alanine aminotransferase) ≤2.5 times the ULN for the clinical laboratory at Screening.
  • Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study.
  • Following receipt of verbal and written information about the study,the patient must provide signed informed consent before any study related activity is carried out.

Who cannot join

  • Evidence of brain metastases, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: to minimize possibility of serious acute flare reactions that would necessitate concomitant administration of other drugs).
  • Evidence of spinal cord compression, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
  • Evidence of severe urinary tract obstruction with threatening urinary retention, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
  • Presence of any tumor in the immediate vicinity that could cause spinal cord compression, in the opinion of the investigator, taking into account medical history and clinical observations (rationale: see rationale in criterion 1).
  • Excruciating, severe pain from extensive osseous deposits, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
  • Testosterone levels <1.5 ng/mL at Screening, This testosterone level will be locally determined at the laboratory of each clinical site (rationale: to ensure that all patients have normal baseline testosterone levels).
Show all 31Show fewer
  • Previous androgen ablative therapy lasting more than 6 months, such as LHRH analogues (e.g., Leuprolide acetate, Goserelin, Buserelin) or antagonists (degarelix). Also, therapy must have not occurred within 12 months before the screening visit. Any prior ADT must have not exceeded 6 months of therapy.
  • Previous treatment with androgen-receptor blockers, such as Bicalutamide, Flutamide, Megestrol acetate, Ciproterone will only be allowed after a 3 month washout prior to the screening visit (rationale: these therapies alter a patient's androgenic hormonal response for a sustained period).
  • Previous orchiectomy, adrenalectomy, or hypophysectomy (no washout allowed) (rationale: these therapies could have altered a patient's androgenic hormonal response).
  • Previous prostatic surgery (e.g., radical prostatectomy, transurethral resection of the prostate) within 2 weeks before Baseline (rationale: these therapies could have altered a patient's androgenic hormonal response and/or adverse reaction profile).
  • Previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks before Baseline (rationale: these therapies could have altered a patient's adverse reaction profile).
  • Previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g., antibody therapies, tumor vaccines), biological response modifiers (e.g., cytokines).
  • Any investigational drug within 5 half-lives of its physiological action or 3 months, whichever is longer, before Baseline (rationale: to prevent adverse effects of another drug being attributed to study drug and to prevent potential interactions).
  • Administration of 5-α-reductase inhibitors (Finasteride, Dutasteride) within 3 months before Baseline (rationale: alters PSA levels and androgen metabolism of the prostate cells). Prior use of 5-α-reductase inhibitors will be allowed with a 3 month washout.
  • Over-the-counter or alternative medical therapies that have an estrogenic or antiandrogenic effect (i.e., PC-SPES, saw palmetto, Glycyrrhiza, Urinozinc, dehydroepiandrosterone) within the 3 months before Baseline.
  • Hematological parameters (red blood cells, total and differential white blood cell count, platelet count, hemoglobin, hematocrit) outside 20% of the ULN or lower limits of normal for the clinical laboratory at Screening (rationale: to render potential study drug-related laboratory abnormalities easier to observe).
  • Coexistent malignancy, in the opinion of the investigator (rationale: to decrease possibility of disease-caused or associated therapy-caused adverse effects being attributed to study drug).
  • Uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure (e.g., balloon angioplasty, coronary artery bypass graft) or significant symptomatic cardiovascular disease(s) within 6 months before Baseline; resting uncontrolled hypertension (≥160/100 mm Hg) or symptomatic hypotension within 3 months before Baseline (rationale: to decrease possibility of disease-caused or associated therapy-caused adverse effects being attributed to study drug).
  • Venous thrombosis within 6 months of Baseline (rationale: influencing testosterone levels may be associated with increased likelihood of deep venous thrombosis).
  • Uncontrolled diabetes, in the opinion of the investigator (rationale:
  • patients with uncontrolled diabetes need to compensate the metabolic disorder before treatment with LHRH analogues).
  • History of drug and/or alcohol abuse within 6 months of Baseline (rationale: these patients are likely to have numerous medical abnormalities and are unlikely to comply with protocol).
  • Serious concomitant illness(es) or disease(s) (e.g., hematological, renal, hepatic, respiratory, endocrine, psychiatric) that may interfere with, or put patients at additional risk for, their ability to receive the treatment outlined in the protocol (rationale: to decrease possibility of disease-caused or associated therapy-caused adverse effects being attributed to study drug).
  • Patients on anticoagulative therapy including warfarin (Coumadin®), Dabigatran Etexilate (Pradaxa®) and heparin. Those patients on low-dose, low-molecular weight heparin may be enrolled in the study (rationale: to decrease possibility of disease-caused or associated therapy-caused adverse effects being attributed to study drug). Plavix and Aspirin are allowed for cardiac prophylaxis as long as all inclusion/exclusion criteria are met concerning coagulation parameters and thromboembolic history. Special care to avoid hematoma at the injection site must be observed.
  • Abnormal coagulation studies (prothrombin time [PT]/partial thromboplastin time [PTT]) at Baseline.
  • History of serious bleeding on injections, an elevated INR, concomitant medications or any other condition (i.e. significant thrombocytopenia) that in opinion of the investigator would render the subject at risk of significant bleeding with injections.
  • Blood donations/losses within 2 months of Baseline, apart from previous prostatic surgery patients (see exclusion 10 [rationale: to avoid excessive blood donations]).
  • Known hypersensitivity to GnRH, GnRH agonists, including any LHRH analogues, or any excipients of the study formulation (rationale: to minimize hypersensitivity reaction to study drug).
  • History of Immunization (within 4 weeks of Baseline) and specifically flu shots (within 1 week of Baseline or 1 week before and after study drug administration) (Rationale: to decrease the possibility of non treatment-related AEs being attributed to study drug).
  • Skin disease that would interfere with injection site evaluation.
  • Men not willing to use appropriate birth control methods such as surgical sterilization or barrier contraception or men with partners of child bearing potential not willing to use appropriate birth control methods, such as surgical sterilization, hormonal birth control (partner), an intrauterine device (partner) or double-barrier method for the entire study period.

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites

  • The Urological Institute of Northeastern New York

    Albany, New York, 12208

  • Urologic Consultants of SE PA

    Bala-Cynwyd, Pennsylvania, 19004

  • Brooklyn Urology Research Group

    Brooklyn, New York, 11215

  • Urology Health Specialists, LLC

    Bryn Mawr, Pennsylvania, 19010

  • Seattle Urology Research Center

    Burien, Washington, 98166

  • North Idaho Urology

    Coeur d'Alene, Idaho, 83814

  • Atlantic Urological Associates

    Daytona Beach, Florida, 32114

  • Mid Atlantic Clinical Research

    Greenbelt, Maryland, 20770

  • Greenville Health System

    Greer, South Carolina, 29650

  • First Urology

    Jeffersonville, Indiana, 47130

  • Premier Urology Associates, LLC

    Lawrenceville, New Jersey, 08648

  • Idaho Urologic Institute

    Meridian, Idaho, 83642

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

  • Urology Associates, PC

    Nashville, Tennessee, 37209

  • Manhattan Medical Research

    New York, New York, 10016

  • Urology Health Team

    Ocala, Florida, 34474

  • Winter Park Urology Associates, PA

    Orlando, Florida, 32803

  • The Premier Medical Group of the Hudson Valley, PC

    Poughkeepsie, New York, 12601

  • Urology San Antonio Research, PA

    San Antonio, Texas, 78229

  • Genesis Research

    San Diego, California, 92123

  • Coastal Medical Center

    Sarasota, Florida, 34237

  • Staten Island Urological Research, PC

    Staten Island, New York, 10304

  • Urology of Virginia

    Virginia Beach, Virginia, 23462

  • PMG Research of Wilmington

    Wilmington, North Carolina, 28401

  • PMG Research of Winston Salem

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: Efficacy and Safety of a New Leuprolide Acetate 22.5 mg Depot Formulation in the Treatment of Prostate Cancer

Some patients with prostate cancer benefit from androgen deprivation therapy which reduces levels of testosterone. Leuprolide is a synthetic Luteinizing hormone releasing hormone (LHRH) analogue which upon administration can decrease testosterone levels to ≤0.5 ng/mL. Leuprolide Acetate 22.5 mg Depot is a microencapsulated formulation of leuprolide which is released slowly over time and effectively reduces testosterone levels in many patients to ≤0.5 ng/mL for up to three months. In this study Leuprolide acetate 22.5 mg Depot will be administered by intramuscular injection twice over a period of 6 months. The proportion of patients with testosterone ≤0.5 ng/mL evaluated over a period of 168 days.

Read the detailed description

This in an open-label, multicenter, multiple-dose investigation of 2 doses of leuprolide acetate 22.5 mg administered with a 3-month interval to patients with histologically proven carcinoma of prostate who might benefit from medical androgen deprivation therapy. A total of up to 160 male patients will receive their first single intramuscular injection of leuprolide acetate 22.5 mg on Day 0 (after baseline assessment) and then after 3 months (Day 84). The study duration will be 6 months. Thirty(30) patients will be screened per protocol and enrolled at selected centers to form the PK cohort. The PK/PD analysis will be performed using plasma specimens from the first 20 of 30 patients enrolled in the study (and included in the PK/PD cohort). Patients not belonging to the PK cohort will be screened and enrolled per protocol and will follow the same study schedule as those enrolled in the PK portion of the study, except they will provide only sparse PK sampling.

Conditions
Prostate Cancer
Being tested
Leuprolide acetate 22.5 mg depot, GP-Pharm SA
Keywords
Prostate Cancer, androgen deprivation therapy., Leuprolide Acetate Depot Formulation, Pharmacokinetics, testosterone, serum luteinizing hormone, follicle-stimulating hormone, prostate-specific antigen
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Leuprolide acetate 22.5 mg depot, GP-Pharm SADrug

    Administered by im injection, twice during the study, three months apart

Study groups in NCT01415960
Study groupRoleWhat they receive
Leuprolide acetate 22.5 mg depotExperimentalLeuprolide acetate 22.5 mg depot administered twice, 3 months apart
Receives: Drug: Leuprolide acetate 22.5 mg depot, GP-Pharm SA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168.

    The primary endpoint was testosterone ≤ 0.5 ng/mL assessed on Days 28, 84, and 168. Thereby, maintenance of castration was to be demonstrated through Day 168 with no missing data at these key time points, unless the missing data were due to an event unrelated to the study drug (ITT patients).

    Measured: 168 days

Secondary outcomes (6)

  1. Determination of Serum Luteinizing Hormone (LH)

    For purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=2.00). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.

    Measured: 168 days

  2. Follicle-stimulating Hormone (FSH)

    For purposes of calculating summary statistics, any concentration values Below Limit of Quantification (BLQ) were to be assigned ½ the Low Limit of Quantification (LLOQ) (LLOQ=3.66). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was to be calculated for that time point.

    Measured: 168 days

  3. Prostate-specific Antigen (PSA) Concentrations

    For purposes of calculating summary statistics, any concentration values Below Limit Quantification (BLQ) were to be assigned ½ the Low Limit Quantification (LLOQ) (LLOQ=0.36). If the calculated mean, median or minimum value at a time point was less than LLOQ, "BLQ" is presented. In addition, since a high proportion of BLQ values may affect the Standard Deviation (SD); if more than 50% of values were imputed, then no mean or median was calculated for that time point.

    Measured: 168 days

  4. Determination of Leuprolide Cmax

    Leuprolide Pharmacokinetic Parameters (PK Population).

    Measured: Cmax1: 0, 1 and 4 hours post-dose on Day 0 and once on Days 2, 14, 28, 56; Cmax2: 0, 1 and 4 hours post-dose on Day 84 and once on Days 86, 112 and 168.

  5. Safety Endpoints

    The WHO/ECOG, bone pain, urinary pain and urinary symptoms data reported are the most frequent percentage at the assessment time.

    • The WHO/ECOG performance status was summarized using the 0 to 4 WHO/ECOG performance status scale. (0= fully active, able to carry on all pre-disease performances without restriction).
    • Bone pain, urinary pain and urinary symptoms were determined using a 10-point scale (1= no pain/symptoms, 10= worst pain/symptom imaginable).

    Measured: 168 Days

  6. Determination of Leuprolide Tmax

    Leuprolide Pharmacokinetic Parameters (PK Population).

    Measured: 84 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Aug 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionMay 2013
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
163 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01415960
Sponsor's protocol ID
GP/C/05/PRO
Status last verified
Nov 2016
First submitted
11 Aug 2011
Last updated
3 Mar 2017
Data monitoring committee
No

Publications

  • Shore ND, Guerrero S, Sanahuja RM, Gambus G, Parente A. A New Sustained-release, 3-Month Leuprolide Acetate Formulation Achieves and Maintains Castrate Concentrations of Testosterone in Patients With Prostate Cancer. Clin Ther. 2019 Mar;41(3):412-425. doi: 10.1016/j.clinthera.2019.01.004. Epub 2019 Feb 8.

    PubMed 30929678

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Leuprolide acetate 22.5 mg depot, GP-Pharm SA in people with Prostate Cancer, run by GP-Pharm at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168. (time frame: 168 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01415960, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in