A Study of Leuprolide to Treat Prostate Cancer

Condition(s) targeted: Prostate Cancer

Intervention: Leuprolide acetate - Formulation A (Drug); Leuprolide acetate - Formulation B (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Abbott

Official(s) and/or principal investigator(s):
Kristof Chwalisz, MD, PhD, Study Director, Affiliation: Abbott

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.

Official title: 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

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

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.

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

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

Secondary outcome:

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

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

Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population

Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population

Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population

Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population

Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population

Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population

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).

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

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.

Site Reference ID/Investigator# 8696, Birmingham, Alabama 35209, United States

Site Reference ID/Investigator# 8681, Homewood, Alabama 35209, United States

Site Reference ID/Investigator# 8569, Anchorage, Alaska 99508, United States

Site Reference ID/Investigator# 9709, Phoenix, Arizona 85013, United States

Site Reference ID/Investigator# 8662, Sierra Vista, Arizona 85635, United States

Site Reference ID/Investigator# 8656, Tucson, Arizona 85710, United States

Site Reference ID/Investigator# 9705, Little Rock, Arkansas 72211, United States

Site Reference ID/Investigator# 8691, Anaheim, California 92801, United States

Site Reference ID/Investigator# 8566, Atherton, California 94027, United States

Site Reference ID/Investigator# 8686, Fresno, California 93720, United States

Site Reference ID/Investigator# 8698, Laguna Hills, California 92653, United States

Site Reference ID/Investigator# 9703, Long Beach, California 90806, United States

Site Reference ID/Investigator# 8674, Los Angeles, California 90015, United States

Site Reference ID/Investigator# 8650, Tarzana, California 91356, United States

Site Reference ID/Investigator# 8699, Torrance, California 90505, United States

Site Reference ID/Investigator# 8668, Denver, Colorado 80211, United States

Site Reference ID/Investigator# 8646, Englewood, Colorado 80113, United States

Site Reference ID/Investigator# 8652, Middlebury, Connecticut 06762, United States

Site Reference ID/Investigator# 8697, New Britain, Connecticut 06052, United States

Site Reference ID/Investigator# 8655, Aventura, Florida 33180, United States

Site Reference ID/Investigator# 8648, Daytona Beach, Florida 32114, United States

Site Reference ID/Investigator# 8660, New Smyrna Beach, Florida 32168, United States

Site Reference ID/Investigator# 8658, Orange City, Florida 32763, United States

Site Reference ID/Investigator# 8664, Orlando, Florida 32803, United States

Site Reference ID/Investigator# 8651, Saint Augustine, Florida 32086, United States

Site Reference ID/Investigator# 8661, St. Petersburg, Florida 33710, United States

Site Reference ID/Investigator# 8568, Tallahassee, Florida 32308, United States

Site Reference ID/Investigator# 8679, Wellington, Florida 33414, United States

Site Reference ID/Investigator# 8562, West Palm Beach, Florida 33407, United States

Site Reference ID/Investigator# 8670, Roswell, Georgia 30076, United States

Site Reference ID/Investigator# 9708, Thomasville, Georgia 31799, United States

Site Reference ID/Investigator# 8693, Fort Wayne, Indiana 46825, United States

Site Reference ID/Investigator# 8690, Newburgh, Indiana 47630, United States

Site Reference ID/Investigator# 8565, Overland Park, Kansas 66211, United States

Site Reference ID/Investigator# 8676, Greenbelt, Maryland 20770, United States

Site Reference ID/Investigator# 8653, Las Vegas, Nevada 89148, United States

Site Reference ID/Investigator# 8667, Lawrenceville, New Jersey 08648, United States

Site Reference ID/Investigator# 9702, Bronx, New York 10461, United States

Site Reference ID/Investigator# 8665, New York, New York 10016, United States

Site Reference ID/Investigator# 8657, Poughkeepsie, New York 12601, United States

Site Reference ID/Investigator# 8680, Charlotte, North Carolina 28209, United States

Site Reference ID/Investigator# 8673, Concord, North Carolina 28025, United States

Site Reference ID/Investigator# 8666, Raleigh, North Carolina 27607, United States

Site Reference ID/Investigator# 8570, Salisbury, North Carolina 28144, United States

Site Reference ID/Investigator# 8644, Winston-Salem, North Carolina 27103, United States

Site Reference ID/Investigator# 8663, Cincinnati, Ohio 45212, United States

Site Reference ID/Investigator# 8567, Columbus, Ohio 43220, United States

Site Reference ID/Investigator# 8678, Bethany, Oklahoma 73008, United States

Site Reference ID/Investigator# 8563, Bala Cynwyd, Pennsylvania 19004, United States

Site Reference ID/Investigator# 8692, Lancaster, Pennsylvania 17604-3200, United States

Site Reference ID/Investigator# 8689, Myrtle Beach, South Carolina 29572, United States

Site Reference ID/Investigator# 8643, Germantown, Tennessee 38138, United States

Site Reference ID/Investigator# 8695, Germantown, Tennessee 38138, United States

Site Reference ID/Investigator# 8685, Memphis, Tennessee 38119, United States

Site Reference ID/Investigator# 8564, Nashville, Tennessee 37209, United States

Site Reference ID/Investigator# 8645, Nashville, Tennessee 37232-2765, United States

Site Reference ID/Investigator# 8641, Dallas, Texas 75231, United States

Site Reference ID/Investigator# 8675, Houston, Texas 77024, United States

Site Reference ID/Investigator# 8684, San Antonio, Texas 78229, United States

Site Reference ID/Investigator# 8649, Tyler, Texas 75701, United States

Site Reference ID/Investigator# 8683, Salt Lake City, Utah 84107, United States

Site Reference ID/Investigator# 8672, Norfolk, Virginia 23502, United States

Site Reference ID/Investigator# 8669, Richmond, Virginia 23235, United States

Starting date: February 2008
Last updated: July 15, 2011