A Study of Leuprolide to Treat Prostate Cancer

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00626431
• Other study ID #: L-PC07-169
• Status: Completed
• Phase: Phase 3
• First received: February 20, 2008
• Last updated: July 15, 2011
• Start date: February 2008
• Est. completion date: September 2009

Study information

• Verified date: July 2011
• Source: Abbott
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 310
• Est. completion date: September 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	Site Reference ID/Investigator# 8691	Anaheim	California
United States	Site Reference ID/Investigator# 8569	Anchorage	Alaska
United States	Site Reference ID/Investigator# 8566	Atherton	California
United States	Site Reference ID/Investigator# 8655	Aventura	Florida
United States	Site Reference ID/Investigator# 8563	Bala Cynwyd	Pennsylvania
United States	Site Reference ID/Investigator# 8678	Bethany	Oklahoma
United States	Site Reference ID/Investigator# 8696	Birmingham	Alabama
United States	Site Reference ID/Investigator# 9702	Bronx	New York
United States	Site Reference ID/Investigator# 8680	Charlotte	North Carolina
United States	Site Reference ID/Investigator# 8663	Cincinnati	Ohio
United States	Site Reference ID/Investigator# 8567	Columbus	Ohio
United States	Site Reference ID/Investigator# 8673	Concord	North Carolina
United States	Site Reference ID/Investigator# 8641	Dallas	Texas
United States	Site Reference ID/Investigator# 8648	Daytona Beach	Florida
United States	Site Reference ID/Investigator# 8668	Denver	Colorado
United States	Site Reference ID/Investigator# 8646	Englewood	Colorado
United States	Site Reference ID/Investigator# 8693	Fort Wayne	Indiana
United States	Site Reference ID/Investigator# 8686	Fresno	California
United States	Site Reference ID/Investigator# 8643	Germantown	Tennessee
United States	Site Reference ID/Investigator# 8695	Germantown	Tennessee
United States	Site Reference ID/Investigator# 8676	Greenbelt	Maryland
United States	Site Reference ID/Investigator# 8681	Homewood	Alabama
United States	Site Reference ID/Investigator# 8675	Houston	Texas
United States	Site Reference ID/Investigator# 8698	Laguna Hills	California
United States	Site Reference ID/Investigator# 8692	Lancaster	Pennsylvania
United States	Site Reference ID/Investigator# 8653	Las Vegas	Nevada
United States	Site Reference ID/Investigator# 8667	Lawrenceville	New Jersey
United States	Site Reference ID/Investigator# 9705	Little Rock	Arkansas
United States	Site Reference ID/Investigator# 9703	Long Beach	California
United States	Site Reference ID/Investigator# 8674	Los Angeles	California
United States	Site Reference ID/Investigator# 8685	Memphis	Tennessee
United States	Site Reference ID/Investigator# 8652	Middlebury	Connecticut
United States	Site Reference ID/Investigator# 8689	Myrtle Beach	South Carolina
United States	Site Reference ID/Investigator# 8564	Nashville	Tennessee
United States	Site Reference ID/Investigator# 8645	Nashville	Tennessee
United States	Site Reference ID/Investigator# 8697	New Britain	Connecticut
United States	Site Reference ID/Investigator# 8660	New Smyrna Beach	Florida
United States	Site Reference ID/Investigator# 8665	New York	New York
United States	Site Reference ID/Investigator# 8690	Newburgh	Indiana
United States	Site Reference ID/Investigator# 8672	Norfolk	Virginia
United States	Site Reference ID/Investigator# 8658	Orange City	Florida
United States	Site Reference ID/Investigator# 8664	Orlando	Florida
United States	Site Reference ID/Investigator# 8565	Overland Park	Kansas
United States	Site Reference ID/Investigator# 9709	Phoenix	Arizona
United States	Site Reference ID/Investigator# 8657	Poughkeepsie	New York
United States	Site Reference ID/Investigator# 8666	Raleigh	North Carolina
United States	Site Reference ID/Investigator# 8669	Richmond	Virginia
United States	Site Reference ID/Investigator# 8670	Roswell	Georgia
United States	Site Reference ID/Investigator# 8651	Saint Augustine	Florida
United States	Site Reference ID/Investigator# 8570	Salisbury	North Carolina
United States	Site Reference ID/Investigator# 8683	Salt Lake City	Utah
United States	Site Reference ID/Investigator# 8684	San Antonio	Texas
United States	Site Reference ID/Investigator# 8662	Sierra Vista	Arizona
United States	Site Reference ID/Investigator# 8661	St. Petersburg	Florida
United States	Site Reference ID/Investigator# 8568	Tallahassee	Florida
United States	Site Reference ID/Investigator# 8650	Tarzana	California
United States	Site Reference ID/Investigator# 9708	Thomasville	Georgia
United States	Site Reference ID/Investigator# 8699	Torrance	California
United States	Site Reference ID/Investigator# 8656	Tucson	Arizona
United States	Site Reference ID/Investigator# 8649	Tyler	Texas
United States	Site Reference ID/Investigator# 8679	Wellington	Florida
United States	Site Reference ID/Investigator# 8562	West Palm Beach	Florida
United States	Site Reference ID/Investigator# 8644	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation A: ITT Population	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	No
Secondary	Mean Testosterone Concentration (+/- Standard Error) at Each Visit for Formulation B: ITT Population	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	No
Secondary	Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation A: ITT Population	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)	No
Secondary	Mean (+/- Standard Error) Acute-on-chronic Changes in Testosterone From Pre-injection Levels for Formulation B: ITT Population	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)	No
Secondary	Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation A: ITT Population	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)	No
Secondary	Mean (+/- Standard Error) Acute-on-chronic Changes in Luteinizing Hormone From Pre-injection Levels for Formulation B: ITT Population	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)	No
Secondary	Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation A: ITT Population	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	No
Secondary	Mean (+/- Standard Error) Prostate Specific Antigen (PSA) at Baseline, Visits Throughout the Study, and at Final Visit for Formulation B: ITT Population	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	No