a study of leuprolide to treat prostate cancer

Conditions: Prostate Cancer

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.

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.

Keywords: lupron depot prostate cancer leuprolide acetate