Clinical trial NCT00223665
Conditions: Prostate Cancer
Keywords: Intermittent Hormone Therapy Intermittent Androgen Suppression Biochemical Relapsed Prostate Cancer Androgen Deprivation Therapy Localized Prostate Cancer
Sponsor: University of Washington
Start date: 1997-01-08; Completion date: 2012-09-06
Enrollment: 102 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This study was a prospective analysis in men with localized prostate cancer who had rising Prostate Specific Antigen (PSA) levels after definitive treatment with surgery or radiation. Patients received Intermittent Androgen Suppression (IAS) in 9 month cycles until they became metastatic, became castrate resistant, or withdrew from the study. Subjects were monitored for time to development of Castration Resistant Prostate Cancer (CRPC) and overall survival. They were also monitored for the impact of IAS on a variety of neuro-psychiatric assessments and on bone density.

Detailed description:
The standard first line treatment for men with early stage newly diagnosed localized prostate cancer is a surgical removal of the prostate, localized external beam radiation, brachytherapy, or a combination of surgery and radiation. In most patients Prostate Specific Antigen (PSA) levels will decline after these localized treatments, demonstrating a response to these therapies. However despite an initial response to localized treatment, some men will go on to later develop a rise in PSA levels, an indicator of Biochemical Relapsed Prostate Cancer (BRPC). For BRPC patients who have not yet developed metastasis, the standard treatment is Androgen Deprivation Therapy (ADT) to decrease levels of Testosterone, subsequently decreasing PSA levels. A low value for the PSA is more desirable as it may indicate no tumor growth.

ADT may be administered as a continuous treatment (Continuous Androgen Suppression, or CAS) or as intermittent treatment (Intermittent Androgen Suppression, or IAS). This treatment is continued until the development of Castration Resistant Prostate Cancer (CRPC), indicated by a rise in PSA despite ADT. Giving the hormone therapy intermittently (in cycles of treatment and off treatment periods) appears to delay the change of prostate cancer to a type of prostate cancer that resists hormone therapy, prolonging efficacy of ADT monotherapy. IAS may also decrease the impact of ADT on mental status.

This study evaluated the effect of intermittent androgen suppression on time to androgen independent progression (the development of castration resistant disease) and overall survival in men with localized prostate cancer. Subjects were also evaluated for the effects of intermittent androgen suppression on a variety of neuro-psychiatric assessments and on bone density.

The subjects in this study had a rising PSA value after definitive therapy either with radical prostatectomy or external beam irradiation for the treatment of prostate cancer. All subjects were males at or over the age of 21 years.

New subjects were introduced to this study protocol (along with other non-study treatment options) during a clinic visit with Dr. Higano or another sub-investigator. After informed consent was obtained, subjects underwent the following screening procedures before starting treatment: Bone density scan (DEXA), Technetium-99 bone scan, CT scan of the chest, abdomen, and pelvis, blood draw, and neuro-psychiatric assessments. Subjects then began androgen suppression with a two-week lead-in of Flutamide, followed by 9 monthly injections of Leuprolide Acetate. During the treatment, they had quarterly clinic visits and blood draws. Their PSA levels were monitored monthly, and if their PSA reached the appropriate nadir at by month 9, the androgen suppression was interrupted. At the end of each treatment cycle, subjects underwent another bone density test, blood draw, problem solving test, and neuro-psychiatric assessments.

During the "off treatment" phase, the subject will again had quarterly clinic visits, blood draws, and neuro-psychiatric assessments. PSA and testosterone were be monitored monthly. Once the PSA reached the appropriate threshold, the subject performed another set of screening procedures and resumed treatment for another 9 months. This cycle continued until the patient withdrew from the study, was taken off the study due to toxicities or the decision of the investigator, or until the treatment with IAS was no longer effective in controlling the prostate cancer. The neuro-psychiatric assessments were only performed during the subject's first cycle of treatment (consisting of the 9 months on treatment, and at month 3 of the off treatment period afterwards).

Arms: arm 1: Intermittent Androgen Suppression in 9 month cycles with a combination of a two-week lead-in of Flutamide, followed by 9 monthly injections of Leuprolide Acetate.

Flutamide dosed as 250mg orally three times a day for 14 days prior to the initiation of Leuprolide Acetate.

Leuprolide Acetate dosed as 7.5mg intramuscular (IM) injections once per month for a total of 9 months.
Interventions: intervention 1: Flutamide intervention 2: Leuprolide Acetate
Intervention descriptions: intervention 1: Flutamide dosed at 250mg orally three times a day for 14 days prior to the initiation of Leuprolide Acetate. intervention 2: Leuprolide Acetate dosed at 7.5mg intramuscular (IM) injections once per month for a total of 9 months.

Protocol documents: