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NCT00223665: IAS

Effects of IAS in Men With Localized Biochemical Relapsed Prostate Cancer

Completed Phase 2 Results posted Last updated 7 August 2018
What this trial tests

Phase 2 trial testing Flutamide in Prostate Cancer in 102 participants. Completed in 6 September 2012.

Timeline
8 January 1997
Primary endpoint
6 September 2012
6 September 2012

Quick facts

Lead sponsorUniversity of Washington
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment102
Start date8 January 1997
Primary completion6 September 2012
Estimated completion6 September 2012
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

University of Washington

Who can join

21 and older, male only, with Prostate Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Time to Androgen Independence of Serum Prostate-Specific Antigen (PSA) Primary · 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.

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.

GroupValue95% CI
Intermittent Androgen Suppression (IAS)4.00.5 – 8.6
Effect of IAS on Overall Survival. Primary · From date of first treatment until the date of death or study withdrawal, whichever came first, assessed up to 16 years.

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

GroupValue95% CI
Intermittent Androgen Suppression (IAS)6.62.9 – 13.0
Change in Standardized Bone Mineral Density (BMD) of the Spine During IAS Secondary · From screening prior to first dose of ADT through the start of the second cycle of ADT.

Dual-energy x-ray absorptiometry (DEXA) scans were performed prior to first cycle of ADT, after completion of the first cycle of ADT, and prior to the start of the second cycle of ADT. Bone Mineral Density (BMD) was a assessed in g/cm\^2 as a indicator of bone health for each patient at each time point.

Post Cycle 1 versus Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)-3.4
Pre Cycle 2 versus Post Cycle 1
GroupValue95% CI
Intermittent Androgen Suppression (IAS)1.4
Change in Standardized Bone Mineral Density (BMD) of the Left Hip During IAS Secondary · From screening prior to first dose of ADT through the start of the second cycle of ADT.

Dual-energy x-ray absorptiometry (DEXA) scans were performed prior to first cycle of ADT, after completion of the first cycle of ADT, and prior to the start of the second cycle of ADT. Bone Mineral Density (BMD) was a assessed in g/cm\^2 as a indicator of bone health. Percent change was assess for each patient at each time point.

Post Cycle 1 versus Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)-1.2
Pre Cycle 2 versus Post Cycle 1
GroupValue95% CI
Intermittent Androgen Suppression (IAS)-0.2
Development of Osteopenia (Bone Loss) During IAS Secondary · From screening prior to first dose of ADT through the start of the second cycle of ADT.

Dual-energy x-ray absorptiometry (DEXA) scans were performed prior to first cycle of ADT, after completion of the first cycle of ADT, and prior to the start of the second cycle of ADT. Bone Mineral Density (BMD) was a assessed in g/cm\^2 as a indicator of bone health for each patient at each time point. This measure was defined as the percentage of participants with normal BMD scores at baseline who developed Osteopenia after the first cycle of ADT.

GroupValue95% CI
Intermittent Androgen Suppression (IAS)13.2
Testosterone Levels During IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Testosterone was measured at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)406± 1.6
Measurement at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)0.28± 0.24
Measurement at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)0.20± 0.07
Measurement at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)2.45± 1.35
Estradiol Levels During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Estradiol was measured at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)33.60± 17.29
Measurement at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)23.12± 6.56
Measurement at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)22.76± 5.75
Measurement at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)24.35± 6.46
Score on Spatial Ability Test (Block Design) During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Spatial Ability was assessed at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT. This assessment was based on the Wechsler Adult Intelligence Scale-Revised, Block Design sub-test and measures participants' ability to analyze and construct abstract figures from their component parts. The test allows a time limit of 3 minutes per design, for a total of nine designs. Score is based on total number of designs completed (max 9, min 0).

Baseline
GroupValue95% CI
Combined Androgen Blockade8.65± 0.81
Score at Month 3
GroupValue95% CI
Combined Androgen Blockade7.20± 1.21
Score at Month 9
GroupValue95% CI
Combined Androgen Blockade8.82± 0.53
Score at Month 12
GroupValue95% CI
Combined Androgen Blockade8.47± 1.06
Score on Spatial Ability Test (Mental Rotation) During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Spatial Ability (Mental Rotation) was assessed at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT. This assessment was based on the Vandenberg \& Kuse (1978) Mental Rotation Test. Subjects are presented with line drawings of complex, three dimensional cubes on a computer screen. The subject must compare the two drawings and decide if they match. Score is based on number of correctly identified figures.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)16.12± 3.39
Score at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)13.00± 3.01
Score at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)16.52± 2.42
Score at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)15.53± 3.08
Score on Executive Function Testing (Stroop Task) During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Executive Function was assessed at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT. This assessment was based on the Stroop Color Word Interference Task. Subjects are asked to read 100 color words (red, green, blue), followed by identification of color blocks followed by reading the color of the ink and ignoring the word (e.g., the word 'blue' printed in green letters). Assessment was based on the amount of time needed to time to complete the assessment.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)51.00± 18.15
Score at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)55.52± 22.11
Score at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)47.58± 11.64
Score at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)48.82± 13.31
Score on Verbal Memory Testing (Proactive Interference) During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Verbal Memory was assessed at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT via the Proactive Interference (PI) task. The PI task involves participants listening to a list of 10 words from the same semantic category (e.g., articles of clothing), and then recalling as many of these words as possible.The procedure is repeated for a total of 4 trials. Assessment is based on the total number of words recalled.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)21.31± 5.50
Score at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)22.90± 5.03
Score at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)22.70± 5.33
Score at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)22.70± 4.33
Score on Visual Working Memory Test During First Cycle of IAS Secondary · Baseline, Month 3, Month 9, and Month 12

Visual Working Memory was assessed at baseline, and at Month 3, Month 9, and Month 12 after the start of the first cycle of ADT. This task is based on the Subject Ordered Pointing Task (SOPT). The participant is shown a grid array of 10, 12 or 16 abstract designs and they must choose a new design with each refresh of the screen. Assessment is based on total number of errors.

Baseline
GroupValue95% CI
Intermittent Androgen Suppression (IAS)13.22± 9.70
Score at Month 3
GroupValue95% CI
Intermittent Androgen Suppression (IAS)15.66± 8.50
Score at Month 9
GroupValue95% CI
Intermittent Androgen Suppression (IAS)12.35± 10.16
Score at Month 12
GroupValue95% CI
Intermittent Androgen Suppression (IAS)14.00± 11.04

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected for each patient from the start of treatment until discontinuation from the study, an average of 16 years per patient.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Combined Androgen Blockade
Serious: 5/102 (5%)
Deaths: 33/102

Serious adverse events (6 terms)

ReactionSystemCombined Androgen Blockade
pnemoniaRespiratory, thoracic and mediastinal disorders
GI bleedGastrointestinal disorders
Atrioventricular node ablationCardiac disorders
exacerbation of claudicationMusculoskeletal and connective tissue disorders
strokeNervous system disorders
left hip painMusculoskeletal and connective tissue disorders
Other adverse events (11 terms — click to expand)

ReactionSystemCombined Androgen Blockade
nocturiaRenal and urinary disorders
hot flashesGeneral disorders
urinary incontinenceRenal and urinary disorders
fatigueGeneral disorders
hyperlipidemiaInvestigations
hypertensionCardiac disorders
pain, bone and muscleMusculoskeletal and connective tissue disorders
weight gainGeneral disorders
depressionPsychiatric disorders
osteopeniaMusculoskeletal and connective tissue disorders
renal insufficiencyRenal and urinary disorders

Most-reported serious reactions: pnemonia, GI bleed, Atrioventricular node ablation, exacerbation of claudication, stroke, left hip pain.

Data from ClinicalTrials.gov NCT00223665 adverse events section.

Sponsor's own description

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.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Duration of first off-treatment interval is prognostic for time to castration resistance and death in men with biochemical relapse of prostate cancer treated on a prospective trial of intermittent androgen deprivation.
    Yu EY, Gulati R, Telesca D, Jiang P, et al · · 2010 · cited 49× · PMID 20421544 · DOI 10.1200/jco.2009.25.1330
  2. Long-term dynamics of bone mineral density during intermittent androgen deprivation for men with nonmetastatic, hormone-sensitive prostate cancer.
    Yu EY, Kuo KF, Gulati R, Chen S, et al · · 2012 · cited 22× · PMID 22493411 · DOI 10.1200/jco.2011.38.3745
  3. Review of Current Treatment Intensification Strategies for Prostate Cancer Patients.
    Wasim S, Park J, Nam S, Kim J. · · 2023 · cited 14× · PMID 38067321 · DOI 10.3390/cancers15235615
  4. Personalizing Androgen Suppression for Prostate Cancer Using Mathematical Modeling.
    Hirata Y, Morino K, Akakura K, Higano CS, et al · · 2018 · cited 13× · PMID 29422657 · DOI 10.1038/s41598-018-20788-1
  5. 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.
    Kuo KF, Hunter-Merrill R, Gulati R, Hall SP, et al · · 2015 · cited 12× · PMID 25242417 · DOI 10.1016/j.clgc.2014.08.003
  6. Intermittent Androgen Suppression: Estimating Parameters for Individual Patients Based on Initial PSA Data in Response to Androgen Deprivation Therapy.
    Hirata Y, Morino K, Akakura K, Higano CS, et al · · 2015 · cited 5× · PMID 26107379 · DOI 10.1371/journal.pone.0130372

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