A Study of Leuprolide to Treat Prostate Cancer

NCT00626431 | Completed Phase 3 Results

• 1 other identifier: L-PC07-169
• Study Type: interventional
• Target: 310
• Locations: 1 country
• Sites: 63

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

Lupron Depot; prostate cancer; leuprolide acetate

Outcome Measures

Primary Outcomes (3)

• 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.

  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

  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

  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 Outcomes (8)

• Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population

  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

  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

  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

  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

  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)

Study Arms (2)

Leuprolide acetate - Formulation A

EXPERIMENTAL

Leuprolide acetate 45 mg, 6-month depot

Drug: Leuprolide acetate - Formulation A

Leuprolide acetate - Formulation B

EXPERIMENTAL

Leuprolide acetate, 45 mg, 6-month depot

Drug: Leuprolide acetate - Formulation B

Interventions

Leuprolide acetate - Formulation A DRUG

Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation A, 45 mg 6 month depot, 24 weeks apart.

Also known as: Lupron, leuprorelin, gonadotropin hormone-releasing hormone (GnRH), luteinizing hormone-releasing hormone (LHRH)

Leuprolide acetate - Formulation A

Leuprolide acetate - Formulation B DRUG

Leuprolide acetate was administered as 2 intramuscular (IM) injections of Formulation B, 45 mg 6 month depot, 24 weeks apart.

Also known as: Lupron, leuprorelin, gonadotropin hormone-releasing hormone (GnRH), luteinizing hormone-releasing hormone (LHRH)

Leuprolide acetate - Formulation B

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abbott: lead

Study Sites (63)

Site Reference ID/Investigator# 8696

Birmingham, Alabama, 35209, United States

Location

Site Reference ID/Investigator# 8681

Homewood, Alabama, 35209, United States

Location

Site Reference ID/Investigator# 8569

Anchorage, Alaska, 99508, United States

Location

Site Reference ID/Investigator# 9709

Phoenix, Arizona, 85013, United States

Location

Site Reference ID/Investigator# 8662

Sierra Vista, Arizona, 85635, United States

Location

Site Reference ID/Investigator# 8656

Tucson, Arizona, 85710, United States

Location

Site Reference ID/Investigator# 9705

Little Rock, Arkansas, 72211, United States

Location

Site Reference ID/Investigator# 8691

Anaheim, California, 92801, United States

Location

Site Reference ID/Investigator# 8566

Atherton, California, 94027, United States

Location

Site Reference ID/Investigator# 8686

Fresno, California, 93720, United States

Location

Site Reference ID/Investigator# 8698

Laguna Hills, California, 92653, United States

Location

Site Reference ID/Investigator# 9703

Long Beach, California, 90806, United States

Location

Site Reference ID/Investigator# 8674

Los Angeles, California, 90015, United States

Location

Site Reference ID/Investigator# 8650

Tarzana, California, 91356, United States

Location

Site Reference ID/Investigator# 8699

Torrance, California, 90505, United States

Location

Site Reference ID/Investigator# 8668

Denver, Colorado, 80211, United States

Location

Site Reference ID/Investigator# 8646

Englewood, Colorado, 80113, United States

Location

Site Reference ID/Investigator# 8652

Middlebury, Connecticut, 06762, United States

Location

Site Reference ID/Investigator# 8697

New Britain, Connecticut, 06052, United States

Location

Site Reference ID/Investigator# 8655

Aventura, Florida, 33180, United States

Location

Site Reference ID/Investigator# 8648

Daytona Beach, Florida, 32114, United States

Location

Site Reference ID/Investigator# 8660

New Smyrna Beach, Florida, 32168, United States

Location

Site Reference ID/Investigator# 8658

Orange City, Florida, 32763, United States

Location

Site Reference ID/Investigator# 8664

Orlando, Florida, 32803, United States

Location

Site Reference ID/Investigator# 8651

Saint Augustine, Florida, 32086, United States

Location

Site Reference ID/Investigator# 8661

St. Petersburg, Florida, 33710, United States

Location

Site Reference ID/Investigator# 8568

Tallahassee, Florida, 32308, United States

Location

Site Reference ID/Investigator# 8679

Wellington, Florida, 33414, United States

Location

Site Reference ID/Investigator# 8562

West Palm Beach, Florida, 33407, United States

Location

Site Reference ID/Investigator# 8670

Roswell, Georgia, 30076, United States

Location

Site Reference ID/Investigator# 9708

Thomasville, Georgia, 31799, United States

Location

Site Reference ID/Investigator# 8693

Fort Wayne, Indiana, 46825, United States

Location

Site Reference ID/Investigator# 8690

Newburgh, Indiana, 47630, United States

Location

Site Reference ID/Investigator# 8565

Overland Park, Kansas, 66211, United States

Location

Site Reference ID/Investigator# 8676

Greenbelt, Maryland, 20770, United States

Location

Site Reference ID/Investigator# 8653

Las Vegas, Nevada, 89148, United States

Location

Site Reference ID/Investigator# 8667

Lawrenceville, New Jersey, 08648, United States

Location

Site Reference ID/Investigator# 8665

New York, New York, 10016, United States

Location

Site Reference ID/Investigator# 8657

Poughkeepsie, New York, 12601, United States

Location

Site Reference ID/Investigator# 9702

The Bronx, New York, 10461, United States

Location

Site Reference ID/Investigator# 8680

Charlotte, North Carolina, 28209, United States

Location

Site Reference ID/Investigator# 8673

Concord, North Carolina, 28025, United States

Location

Site Reference ID/Investigator# 8666

Raleigh, North Carolina, 27607, United States

Location

Site Reference ID/Investigator# 8570

Salisbury, North Carolina, 28144, United States

Location

Site Reference ID/Investigator# 8644

Winston-Salem, North Carolina, 27103, United States

Location

Site Reference ID/Investigator# 8663

Cincinnati, Ohio, 45212, United States

Location

Site Reference ID/Investigator# 8567

Columbus, Ohio, 43220, United States

Location

Site Reference ID/Investigator# 8678

Bethany, Oklahoma, 73008, United States

Location

Site Reference ID/Investigator# 8563

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Site Reference ID/Investigator# 8692

Lancaster, Pennsylvania, 17604-3200, United States

Location

Site Reference ID/Investigator# 8689

Myrtle Beach, South Carolina, 29572, United States

Location

Site Reference ID/Investigator# 8643

Germantown, Tennessee, 38138, United States

Location

Site Reference ID/Investigator# 8695

Germantown, Tennessee, 38138, United States

Location

Site Reference ID/Investigator# 8685

Memphis, Tennessee, 38119, United States

Location

Site Reference ID/Investigator# 8564

Nashville, Tennessee, 37209, United States

Location

Site Reference ID/Investigator# 8645

Nashville, Tennessee, 37232-2765, United States

Location

Site Reference ID/Investigator# 8641

Dallas, Texas, 75231, United States

Location

Site Reference ID/Investigator# 8675

Houston, Texas, 77024, United States

Location

Site Reference ID/Investigator# 8684

San Antonio, Texas, 78229, United States

Location

Site Reference ID/Investigator# 8649

Tyler, Texas, 75701, United States

Location

Site Reference ID/Investigator# 8683

Salt Lake City, Utah, 84107, United States

Location

Site Reference ID/Investigator# 8672

Norfolk, Virginia, 23502, United States

Location

Site Reference ID/Investigator# 8669

Richmond, Virginia, 23235, United States

Location

Related Publications (1)

• Spitz A, Young JM, Larsen L, Mattia-Goldberg C, Donnelly J, Chwalisz K. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012 Mar;15(1):93-9. doi: 10.1038/pcan.2011.50. Epub 2011 Oct 25.

  PMID: 22025196 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide; Gonadotropin-Releasing Hormone

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)

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

Limitations and Caveats

Treatment with Formulation B was prematurely discontinued as testosterone was not adequately suppressed to \<= 50 ng/dL or escapes from suppression occurred. Subjects who had not received dose 2 of Formulation B were discontinued after Week 24.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Kristof Chwalisz, MD, PhD

  Abbott

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 29, 2008
• Study Start: February 1, 2008
• Primary Completion: August 1, 2009
• Study Completion: September 1, 2009
• Last Updated: July 19, 2011
• Results First Posted: November 1, 2010

Record last verified: 2011-07

Locations

US (63)