Effects of IAS in Men With Localized Biochemical Relapsed Prostate Cancer

NCT00223665 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: 30296973730AC06HSD 30296
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

Intermittent Hormone Therapy; Intermittent Androgen Suppression; Biochemical Relapsed Prostate Cancer; Androgen Deprivation Therapy; Localized Prostate Cancer

Outcome Measures

Primary Outcomes (2)

• Time to Androgen Independence of Serum Prostate-Specific Antigen (PSA)

  Monthly Prostate-Specific Antigen (PSA) testing to assess the point at which each patient's disease stops responding to Androgen Deprivation Therapy (ADT). Androgen Independence (AI), also know as Castrate Resistance (CR), was defined as 2 serial rises in PSA while on ADT with Testosterone levels \<50 ng/dL.

  From date of first treatment until the date of development of CR, metastatic progression, or study withdrawal, whichever came first, assessed up to 16 years.

• Effect of IAS on Overall Survival.

  Assessment of overall survival measured as median time from completion of first full cycle of IAS until date of death from any cause.

  From date of first treatment until the date of death or study withdrawal, whichever came first, assessed up to 16 years.

Secondary Outcomes (13)

• Change in Standardized Bone Mineral Density (BMD) of the Spine During IAS

  From screening prior to first dose of ADT through the start of the second cycle of ADT.

• Change in Standardized Bone Mineral Density (BMD) of the Left Hip During IAS

  From screening prior to first dose of ADT through the start of the second cycle of ADT.

• Development of Osteopenia (Bone Loss) During IAS

  From screening prior to first dose of ADT through the start of the second cycle of ADT.

• Testosterone Levels During IAS

  Baseline, Month 3, Month 9, and Month 12

• Estradiol Levels During First Cycle of IAS

  Baseline, Month 3, Month 9, and Month 12

Study Arms (1)

Intermittent Androgen Suppression (IAS)

EXPERIMENTAL

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.

Drug: Flutamide; Drug: Leuprolide Acetate

Interventions

Flutamide DRUG

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

Also known as: Eulexin

Intermittent Androgen Suppression (IAS)

Leuprolide Acetate DRUG

Leuprolide Acetate dosed at 7.5mg intramuscular (IM) injections once per month for a total of 9 months.

Also known as: Lupron Depot, Eligard, Lupron

Intermittent Androgen Suppression (IAS)

Eligibility Criteria

• Age: 21 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Biochemical relapse (rising PSA) after initial treatment (radiation therapy, brachytherapy, or radical prostatectomy) for histologically or cytologically confirmed adenocarcinoma of the prostate
• Clinical stage A2, B, C, D1
• Age: older than 21 years old
• Performance status of 0 or 1
• Pretreatment serum testosterone, normal range (or no clinical evidence of testosterone deficiency).
• If less than 30 months since completion of radiation therapy, biopsy of prostate suggested within 6 months of study entry. If more than or equal to 30 months since completion of radiation therapy, biopsy of prostate suggested within 1 year.
• Written informed consent.

You may not qualify if:

• Abnormal bone scan suggestive of metastatic osseous disease.
• Previous hormonal manipulation including orchiectomy or any medication with significant antiandrogenic activity (combined androgen suppression over 9 months, monotherapy antiandrogens, estrogens, ketoconazole). \*Neoadjuvant androgen suppression therapy of less than or equal to 3 months is allowed, if this androgen suppression therapy was completed more than or equal to 1 year prior to study enrollment AND if the Testosterone level is within the normal ranges.
• Any systemic chemotherapy or curative radiotherapy within 6 months.
• Hepatic dysfunction:
• Total bilirubin greater than 2.0 mg/dl
• Aspartate transaminase (AST; SGOT) greater than 3 times the upper limit of normal range
• Lactate dehydrogenase (LDH) greater than 3 times the upper limit of normal range).
• Renal dysfunction:
• Blood urea nitrogen (BUN) greater than 40 mg/dl
• Serum Creatinine greater than 2.0 mg/dl.
• History or presence of other malignancy within the last 5 years (except treated squamous/basal cell carcinoma of the skin or superficial bladder carcinoma).
• Hypersensitivity to flutamide or leuprolide.

Sponsors & Collaborators

• University of Washington: lead
• Sanofi: collaborator

Study Sites (1)

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Kuo KF, Hunter-Merrill R, Gulati R, Hall SP, Gambol TE, Higano CS, Yu EY. Relationships between times to testosterone and prostate-specific antigen rises during the first off-treatment interval of intermittent androgen deprivation are prognostic for castration resistance in men with nonmetastatic prostate cancer. Clin Genitourin Cancer. 2015 Feb;13(1):10-6. doi: 10.1016/j.clgc.2014.08.003. Epub 2014 Aug 10.

  PMID: 25242417 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Flutamide; Leuprolide; luprolide acetate gel depot

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Celestia Higano, MD
• Organization: University of Washington

mjcampbe@seattlecca.org

206-606-1187

Study Officials

• Celestia Higano, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Medicine, Division of Oncology & Urology

Model Details: All subjects underwent androgen suppression with a two-week lead-in of Flutamide, followed by 9 monthly injections of Leuprolide Acetate. If PSA reached the appropriate nadir at by month 9, the androgen suppression was interrupted. Once the PSA reached the appropriate threshold, the subjects resumed treatment for another 9 months. These 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.

Study Record Dates

• First Submitted: September 16, 2005
• First Posted: September 22, 2005
• Study Start: January 8, 1997
• Primary Completion: September 6, 2012
• Study Completion: September 6, 2012
• Last Updated: August 7, 2018
• Results First Posted: May 14, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)