Clinical trial NCT00626431: A Study of Leuprolide to Treat Prostate Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Lupron Depot
prostate cancer
leuprolide acetate
Lead sponsor: Abbott
Sponsor class: INDUSTRY
First posted: 2008-02-29
Enrollment: 310
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: Week 4 to Week 48
measure: 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
timeFrame: Week 4 to Week 48
measure: 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
timeFrame: Week 4 to Week 48
Secondary outcomes:
measure: Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population
timeFrame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
measure: Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population
timeFrame: Baseline, Days 2 and 8, Weeks 2, 4, 8, 14, 20, 24, 26, 30, 34, 40, 46, 48, and Final Visit
measure: Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population
timeFrame: 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)
measure: Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population
timeFrame: 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)
measure: Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population
timeFrame: 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)
measure: Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population
timeFrame: 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)
measure: Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population
timeFrame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
measure: Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population
timeFrame: Baseline, Day 8, Week 14, Week 24, Week 30, Week 40, Week 48, and the Final Visit
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Site Reference ID/Investigator# 8696
state: Alabama
city: Homewood
country: United States
facility: Site Reference ID/Investigator# 8681
state: Alabama
city: Anchorage
country: United States
facility: Site Reference ID/Investigator# 8569
state: Alaska
city: Phoenix
country: United States
facility: Site Reference ID/Investigator# 9709
state: Arizona
city: Sierra Vista
country: United States
facility: Site Reference ID/Investigator# 8662
state: Arizona
city: Tucson
country: United States
facility: Site Reference ID/Investigator# 8656
state: Arizona
city: Little Rock
country: United States
facility: Site Reference ID/Investigator# 9705
state: Arkansas
city: Anaheim
country: United States
facility: Site Reference ID/Investigator# 8691
state: California
city: Atherton
country: United States
facility: Site Reference ID/Investigator# 8566
state: California
city: Fresno
country: United States
facility: Site Reference ID/Investigator# 8686
state: California
city: Laguna Hills
country: United States
facility: Site Reference ID/Investigator# 8698
state: California
city: Long Beach
country: United States
facility: Site Reference ID/Investigator# 9703
state: California
city: Los Angeles
country: United States
facility: Site Reference ID/Investigator# 8674
state: California
city: Tarzana
country: United States
facility: Site Reference ID/Investigator# 8650
state: California
city: Torrance
country: United States
facility: Site Reference ID/Investigator# 8699
state: California
city: Denver
country: United States
facility: Site Reference ID/Investigator# 8668
state: Colorado
city: Englewood
country: United States
facility: Site Reference ID/Investigator# 8646
state: Colorado
city: Middlebury
country: United States
facility: Site Reference ID/Investigator# 8652
state: Connecticut
city: New Britain
country: United States
facility: Site Reference ID/Investigator# 8697
state: Connecticut
city: Aventura
country: United States
facility: Site Reference ID/Investigator# 8655
state: Florida
city: Daytona Beach
country: United States
facility: Site Reference ID/Investigator# 8648
state: Florida
city: New Smyrna Beach
country: United States
facility: Site Reference ID/Investigator# 8660
state: Florida
city: Orange City
country: United States
facility: Site Reference ID/Investigator# 8658
state: Florida
city: Orlando
country: United States
facility: Site Reference ID/Investigator# 8664
state: Florida
city: Saint Augustine
country: United States
facility: Site Reference ID/Investigator# 8651
state: Florida
city: St. Petersburg
country: United States
facility: Site Reference ID/Investigator# 8661
state: Florida
city: Tallahassee
country: United States
facility: Site Reference ID/Investigator# 8568
state: Florida
city: Wellington
country: United States
facility: Site Reference ID/Investigator# 8679
state: Florida
city: West Palm Beach
country: United States
facility: Site Reference ID/Investigator# 8562
state: Florida
city: Roswell
country: United States
facility: Site Reference ID/Investigator# 8670
state: Georgia
city: Thomasville
country: United States
facility: Site Reference ID/Investigator# 9708
state: Georgia
city: Fort Wayne
country: United States
facility: Site Reference ID/Investigator# 8693
state: Indiana
city: Newburgh
country: United States
facility: Site Reference ID/Investigator# 8690
state: Indiana
city: Overland Park
country: United States
facility: Site Reference ID/Investigator# 8565
state: Kansas
city: Greenbelt
country: United States
facility: Site Reference ID/Investigator# 8676
state: Maryland
city: Las Vegas
country: United States
facility: Site Reference ID/Investigator# 8653
state: Nevada
city: Lawrenceville
country: United States
facility: Site Reference ID/Investigator# 8667
state: New Jersey
city: Bronx
country: United States
facility: Site Reference ID/Investigator# 9702
state: New York
city: New York
country: United States
facility: Site Reference ID/Investigator# 8665
state: New York
city: Poughkeepsie
country: United States
facility: Site Reference ID/Investigator# 8657
state: New York
city: Charlotte
country: United States
facility: Site Reference ID/Investigator# 8680
state: North Carolina
city: Concord
country: United States
facility: Site Reference ID/Investigator# 8673
state: North Carolina
city: Raleigh
country: United States
facility: Site Reference ID/Investigator# 8666
state: North Carolina
city: Salisbury
country: United States
facility: Site Reference ID/Investigator# 8570
state: North Carolina
city: Winston-Salem
country: United States
facility: Site Reference ID/Investigator# 8644
state: North Carolina
city: Cincinnati
country: United States
facility: Site Reference ID/Investigator# 8663
state: Ohio
city: Columbus
country: United States
facility: Site Reference ID/Investigator# 8567
state: Ohio
city: Bethany
country: United States
facility: Site Reference ID/Investigator# 8678
state: Oklahoma
city: Bala Cynwyd
country: United States
facility: Site Reference ID/Investigator# 8563
state: Pennsylvania
city: Lancaster
country: United States
facility: Site Reference ID/Investigator# 8692
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Site Reference ID/Investigator# 8689
state: South Carolina
city: Germantown
country: United States
facility: Site Reference ID/Investigator# 8643
state: Tennessee
city: Germantown
country: United States
facility: Site Reference ID/Investigator# 8695
state: Tennessee
city: Memphis
country: United States
facility: Site Reference ID/Investigator# 8685
state: Tennessee
city: Nashville
country: United States
facility: Site Reference ID/Investigator# 8564
state: Tennessee
city: Nashville
country: United States
facility: Site Reference ID/Investigator# 8645
state: Tennessee
city: Dallas
country: United States
facility: Site Reference ID/Investigator# 8641
state: Texas
city: Houston
country: United States
facility: Site Reference ID/Investigator# 8675
state: Texas
city: San Antonio
country: United States
facility: Site Reference ID/Investigator# 8684
state: Texas
city: Tyler
country: United States
facility: Site Reference ID/Investigator# 8649
state: Texas
city: Salt Lake City
country: United States
facility: Site Reference ID/Investigator# 8683
state: Utah
city: Norfolk
country: United States
facility: Site Reference ID/Investigator# 8672
state: Virginia
city: Richmond
country: United States
facility: Site Reference ID/Investigator# 8669
state: Virginia
Study officials:
affiliation: Abbott
name: Kristof Chwalisz, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.