Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Disease Progression

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Dutasteride

5-alpha Reductase Inhibitors

Enzyme Inhibitors

Hormones

Hormone Antagonists

Matching placebo

GSK Clinical Trials

The purpose of this study is to examine the effect of dutasteride on the inhibition of low-risk, localized prostate cancer progression in men who would otherwise receive no active therapy (expectant management).

Assessment Of Dutasteride (AVODART) In Extending The Time To Progression Of Low-Risk, Localized Prostate Cancer In Men

A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Efficacy and Safety of Dutasteride in Extending the Time to Progression of Low-Risk, Localized Prostate Cancer in Men Who Are Candidates for or Undergoing Expectant Management

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

PC progression (prog.) was defined as the earliest occurrence of primary therapy, also referred to as therapeutic prog., for PC (prostatectomy/radiation/hormonal therapy); or pathological prog., defined as 1 of the following: \>=4 cores involved; \>=50% of any 1 core involved; or a Gleason pattern of \>=4 as a result of any on-study/for-cause biopsy. Primary Gleason grade is assigned to the most common tumor pattern; a second grade to the next most common tumor pattern. The two grades are added together to get a score. Gleason grade= 1-5; Gleason score=2-10; 5 and 10 indicate worst prognosis.

Primary therapy, also referred to as therapeutic progression, for prostate cancer can be one of the following: prostatectomy, radiation, or hormonal therapy.

Pathological progression is defined as one of the following: \>=4 cores involved; \>=50% of any 1 core involved; or a Gleason pattern of \>=4 as a result of any on-study/for-cause biopsy. The 2005 International Society of Urological Pathologists recommendations for Gleason scoring (GS) were used to grade tumors. A primary grade is assigned to the most common tumor pattern, and a second grade to the next most common tumor pattern. The two grades are added together to get a GS. The Gleason grade=1-5, with 5 having the worst prognosis. The Gleason score=2-10, with 10 having the worst prognosis.

All participants were required by protocol to undergo a transrectal ultrasound (TRUS)-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. If a for-cause biopsy occurred within 6 months prior to the protocol-mandated biopsy, the biopsy was counted as the protocol-mandated biopsy. All biopsies were reviewed and analyzed by a central pathologist.

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. If a for-cause biopsy occurred within 6 months prior to the protocol-mandated biopsy, the biopsy was counted as the protocol-mandated biopsy. The final biopsy is defined as the latest post-baseline biopsy for which the results are available from the central pathology laboratory.

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. . The final biopsy is defined as the latest post-baseline biopsy for which the results are available from the central pathology laboratory.

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. Change from baseline was calculated as the number of cancer-positive cores at post-baseline biopsy minus the number of cancer-positive cores at baseline.

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsies (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. The sum of cancer positive cores and the sum of evaluated cores were used to compute the percentage (100\* number of positive cores/number of evaluated cores).

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. (100 \* number of positive cores/number of evaluated cores).

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist. Tumor length is calculated as the number of cores (12) \* total tumor length/number of evaluated cores.

All participants were required by protocol to undergo a TRUS-guided 12-core prostate biopsy at 1.5 and 3 years or at the end of the study, if the participant discontinued the study early. Any for-cause biopsy (outside of protocol-mandated biopsies) 12 cores were obtained. All biopsies were reviewed and analyzed by a central pathologist.

The 2005 International Society of Urological Pathologists recommendations for Gleason scoring were used to grade tumors. A primary grade is assigned to the most common tumor pattern (how the cancer cells look under a microscope), and a second grade to the next most common pattern. The two grades are added together to get a GS. Gleason grade range= 1-5; 5=worst prognosis. GS range=2-10; 10=worst prognosis. Improvement is defined as a decrease in GS from a baseline score of 6 (GS\<=6; includes no cancer); worsening is defined as an increase in GS from a baseline score of 6 (GS \>6).

All on-study or for-cause biopsies were reviewed and analyzed by a central pathologist. The 2005 International Society of Urological Pathologists recommendations for Gleason scoring were used to grade the tumor. A primary grade is assigned to the most common tumor pattern (how the cancer cells look under a microscope), and a secondary grade to the next most common tumor pattern. The two grades are added together to get a GS. The Gleason grade ranges from 1 to 5, with 5 having the worst prognosis. The Gleason score ranges from 2 to 10, with 10 having the worst prognosis.

All on-study or for-cause biopsies were reviewed and analyzed by a central pathologist. The 2005 International Society of Urological Pathologists recommendations for clinical tumor staging were used. T1c = tumor identified by needle biopsy (e.g., because of elevated prostate-specific antigen \[PSA\]); T2 = tumor confined within the prostate; T2a = tumor involves one-half of one lobe, but not both lobes of the prostate.

All on-study or for-cause biopsies were reviewed and analyzed by a central pathologist. The National Comprehensive Network (NCCN), 2005 clinical practices guidelines in Oncology-prostate cancer were used for clinical tumor staging. T0: no evidence of primary tumor; T1: clinically inapparent tumor, neither palpable nor visible by imaging; T2: tumor confined within the prostate; T3: tumor extends through the prostate capsule; T4: tumor is fixed or invades adjacent structures other than seminal vesicles. A clinical stage of T0 in post-baseline biopsies has been interpreted as "No Worsening."

Prostate volume was determined at baseline, at Year 1.5, and at Year 3. The anteroposterior, cephalocaudal, and transverse diameters of the prostate were obtained by transrectal ultrasound (TRUS) to calculate the prostate volume using the following formula:

π/ 6 (anteroposterior width \* cephalocaudal width \* transverse width). Prostate volume calculated by pre-programmed equipment is unacceptable for the on-study prostate volume measurements.

Prostate volume was determined at baseline, Year 1.5, and Year 3. The anteroposterior, cephalocaudal, and transverse diameters of the prostate were obtained by transrectal ultrasound (TRUS) to calculate the prostate volume using the following formula:

π/ 6 (anteroposterior width \* cephalocaudal width \* transverse width). Prostate volume calculated by pre-programmed equipment was unacceptable for the on-study prostate volume measurements.

Prostate volume was determined at baseline, Year 1.5, and Year 3. The anteroposterior, cephalocaudal, and transverse diameters of the prostate were obtained by transrectal ultrasound (TRUS) to calculate the prostate volume using the following formula:

π/ 6 (anteroposterior width \* cephalocaudal width \* transverse width). Prostate volume calculated by pre-programmed equipment is unacceptable for the on-study prostate volume measurements.

The MAX-PC is a self-reported measure evaluating three aspects of PC-related anxiety: general anxiety related to PC/treatment, fear of recurrence, and anxiety related to PSA testing. The MAX-PC consists of 18 questions, each score ranging from 0 (least anxiety) to 3 (maximum anxiety). Total score is the sum of each question score, thus ranging from 0 to 54. A higher MAX-PC score indicates greater anxiety. At Months 18 and 36, participants were given an additional copy of the questionnaire and were asked to complete at home once they were notified of their PSA result and to send back to clinic.

The MAX-PC anxiety subscale consists of 3 questions related to PSA testing; "I have been so anxious about my PSA test that I have thought about delaying it.", "I have been so worried about my PSA test result that I have thought about asking my doctor to repeat the test.", "I have been so concerned about my PSA test result that I have thought about having the test repeated at another laboratory to make sure the test results were accurate." A higher MAX-PC score indicates greater anxiety.Scores range from 0 to 3 for each question. The total score is the sum of the 3 question scores; 0 to 9.

The MAX-PC fear of recurrence subscale consists of 4 questions related to fear of recurrence; "Because cancer is unpredictable, I feel I cannot plan for the future.", "My fear of having my cancer getting worse gets in the way of my enjoying life.", "I am afraid of my cancer getting worse.", "I am more nervous since I was diagnosed with prostate cancer." A higher MAX-PC score indicates greater anxiety. Scores range from 0 to 3 for each question. The total score is the sum of the 4 question scores: 0 to 12.

The FACT-P consists of a total of 39 questions. This scale is divided into five subscales: the Physical Well-Being Subscale (7 questions); the Social/Family Well-Being Subscale (7 questions); the Emotional Well-Being Subscale (6 questions); the Functional Well-Being Subscale (7 questions); and the Prostate Cancer Subscale (12 questions). The score for each of the 39 questions ranges from 0 to 4. The total FACT-P score thus ranges from 0 to156; a higher score indicates better quality of life.

The FACT-P consists of a total of 39 questions. This scale is divided into five subscales: the Physical Well-Being Subscale (7 questions); the Social/Family Well-Being Subscale (7 questions); the Emotional Well-Being Subscale (6 questions); the Functional Well-Being Subscale (7 questions); and the Prostate Cancer Subscale (12 questions). The questionnaire was administered at baseline and at Months 18 and 36. The score for each of the 39 questions ranges from 0 to 4. The total FACT-P score thus ranges from 0 to156; a higher score indicates better QOL.

The FACT-P Physical Well-Being subscale is divided into 7 questions, and the participants rated the outcome over the past 7 days; "I have a lack of energy.", "I have nausea.", "Because of my physical condition, I have trouble meeting the needs of my family.", "I have pain.", "I am bothered by side effects of treatment.", "I feel ill.", "I am forced to spend time in bed." The score for each question ranges from 0 to 4; a lower score indicates better physical well-being. The total FACT-P score thus ranges from 0 to156; a higher score indicates a better quality of life.

The FACT-P Social Well-Being subscale is divided into 7 questions, and the participants rated the outcome over the past 7 days; "I feel close to my friends.", "I get emotional support from my family.", "I get support from my friends.", "My family has accepted my illness.", "I am satisfied with family communication about my illness.", "I feel close to my partner (or the person who is my main support).", "I am satisfied with my sex life." The score for each question ranges from 0 to 4; a higher score indicates better social well-being. The total FACT-P score thus ranges from 0 to 156.

GlaxoSmithKline

Matching placebo 0.5 mg administered orally once daily for 156 weeks

Matching Placebo 0.5 mg Once Daily

Dutasteride 0.5 mg administered orally once daily for 156 weeks

Dutasteride 0.5 mg Once Daily

Total

Age, Continuous

Gender

White

African American

Asian

American Indian or Alaskan Native

Native Hawaiian or Other Pacific Islander

White and American Indian/Alaskan Native

Race/Ethnicity, Customized

GSK Response Center

Year 1.5, n=144, 142

Overall (Years 0-3), n= 155, 147

ITT Population: all participants randomized to study treatment. Some participants dropped out of the study prior to meeting the primary endpoint for reasons other than disease progression or refused to have a biopsy performed.

Number of Participants With Prostate Cancer (PCa) Progression [Restricted Crude Rate Analysis: Number of Participants With PCa Divided by Number of Participants in the Intent-to-Treat (ITT) Population Who Had >=1 Post-baseline Biopsy or Had a Progression

Year 1.5

Overall (Years 0-3)

Number of Participants With Therapeutic Progression

Year 1.5, n= 136, 139

Overall (Years 0-3) n=136, 140

ITT Population. As the study progressed, participants dropped out of the study prior to meeting the primary endpoint for reasons other than disease progression or refused to have a biopsy performed.

Number of Participants With Pathologic Progression

Participants with a PCa diagnosis

Participants with no PCa diagnosis

ITT Population. As the study progressed, participants dropped out of the study.

Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis

Participants With at Least One Post-baseline Biopsy With the Indicated Prostate Cancer (PCa) Diagnosis for Their Final Biopsy

Baseline, n=155, 147

Year 1.5, n=87, 99

Year 3, n=52, 54

Years 0-3 (Final biopsy), n=105, 90

Number of Cancer-positive Cores in a 12-core Biopsy

Year 1.5, n= 87, 99

Change From Baseline in the Number of Cancer-positive Cores in a 12-core Biopsy at Years 1.5, 3, and 0-3

Baseline, n= 155, 147

Mean Percentage of Cancer-positive Cores in a 12-core Biopsy

Change From Baseline in the Percentage of Cancer-positive Cores in a 12-core Biopsy at Years 1.5, 3, and 0-3

Cumulative Length of Cancer Tumor Core

Change From Baseline in the Cumulative Length of Cancer Tumor Core at Years 1.5, 3, and 0-3

Improvement

No change

Worsening

Number of Participants With the Indicated Change From Baseline in Gleason Score (GS) on Repeat Biopsy at Year 1.5

No cancer, GS 0

Number of Participants With the Indicated Change From Baseline in Gleason Score on Repeat Biopsy at Years 0-3

Missing (No Cancer)

GS 5

GS 6

GS 7, 3 (primary grade) + 4 (secondary grade)

GS 7, 4 (primary grade) + 3 (secondary grade)

GS 8

GS 9-10

Number of Participants With the Indicated Total Gleason Score

Number of Biopsies With the Indicated Clinical Tumor Stage at Baseline

No Worsening (same/lower stage)

Worsening (higher stage)

Number of Post-baseline Biopsies With the Indicated Change From Baseline in Clinical Stage

Baseline, n=133, 126

Year 1.5, n=117, 117

Year 3, n=118, 118

ITT Population. As the study progressed, participants dropped out of the study. Last observation carried forward (LOCF) was used.

Prostate Volume (PV) LOCF

Change From Baseline in Prostate Volume at Years 1.5 and 3

Percent Change From Baseline in Prostate Volume at Years 1.5 and 3

Baseline, n=151, 146

Month 3, n=150, 144

Month 6, n=152, 144

Month 12, n=152, 144

Month 18, n=152, 144

Month 18 Take-Home, n=152, 144

Month 36, n=152, 144

Month 36 Take-Home, n=152, 144

ITT Population. As the study progressed, participants dropped out of the study or did not complete the questionnaire.

Total Memorial Anxiety Scale Scores for Prostate Cancer (MAX-PC)

Month 3, n=146, 143

Month 6, n=148, 143

Month 12, n=148, 143

Month 18, n=148, 143

Month 18 Take-Home, n=148, 143

Month 36, n=148, 143

Month 36 Take-Home, n=148, 143

ITT Population. Only participants with both available baseline and post-baseline values were analyzed at the indicated time points. As the study progressed, participants dropped out of the study or did not complete the questionnaire.

Change From Baseline in Total Memorial Anxiety Scale Scores for Prostate Cancer (MAX-PC) LOCF

Baseline, n=154, 147

Month 3, n=152, 144

Month 36, n=152,144

Total MAX-PC Anxiety Subscale Score Related to PSA Testing

Month 3

Month 6

Month 12

Month 18

Month 18 Take-Home

Month 36

Month 36 Take-Home

Change From Baseline in MAX-PC Anxiety Subscale Score Related to PSA Testing (LOCF)

Total MAX-PC Fear of Recurrence Subscale Score

Month 6, n= 148, 143

Change From Baseline in MAX-PC Fear of Recurrence Subscale Score (LOCF)

Baseline, n=154, 145

Month 18, n=145, 140

Month 36, n=149, 140

Total Functional Assessment of Cancer Therapy Scale, Prostate Module (FACT-P) Score

Month 18, n=144, 140

Month 36, n=148, 140

Change From Baseline in Total FACT-P Score (LOCF)

Percent Change From Baseline in Total FACT-P Score (LOCF)

Month 18, n=148, 140

Change From Baseline in FACT-P Physical Well-Being Subscale Score (LOCF)

Change From Baseline in FACT-P Social Well-Being Subscale Score (LOCF)

Matching placebo 0.5 milligrams (mg) administered orally once daily for 156 weeks

Spots Global Cancer Trial Database for dutasteride prostate cancer expectant management redeem