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| ID | Type | Description | Link |
|---|---|---|---|
| UCSF-05551 | Other Identifier | UCSF | |
| H7056-26910-03 | Other Identifier | Committee on Human Research (CHR) |
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RATIONALE: Diagnostic procedures, such as MRI and magnetic resonance spectroscopy imaging, may help in learning how well dutasteride works in patients with benign prostatic hypertrophy and low-risk prostate cancer.
PURPOSE: This clinical trial is studying MRI and magnetic resonance spectroscopy imaging in patients receiving dutasteride for benign prostatic hypertrophy and low-risk prostate cancer.
OBJECTIVES:
Primary
Secondary
OUTLINE: Patients receive oral dutasteride once daily for 6 months.
Patients undergo endorectal MRI and magnetic resonance spectroscopy imaging at baseline and at 1, 3, and 6 months.
Patients complete quality-of-life questionnaires using the International Index of Erectile Function Questionnaire, American Urological Association Symptom Index, Functional Alterations due to Changes in Elimination, and Spitzer Quality-of-Life Index at baseline and at 1, 3, and 6 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dutasteride | Experimental | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dutasteride | Drug | 6 months of dutasteride 3.5 mg daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Change in Extent of Cancer | Proportion of voxels consistent with prostate cancer as measured by magnetic resonance spectroscopy imaging (MRSI). MRSI spectra were examined and scored as healthy or cancerous. The change in cancerous volumes over time was evaluated. Because a significant decrease in citrate and polyamines on MRSI spectra was noted at 1 month compared with baseline, healthy tissue appeared to be more like cancer and thus created a false impression that the cancer had grown after 1 month. To reduce this bias, primary comparisons were made between the 1-month and 6-month scans. | 1 month, 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events Indicative of Safety of Dutasteride | Toxicities from Dutasteride were recorded at each study visit and assessed by NCI-CTCAE v3.0. | Baseline, 1, 3, and 6 months |
| Symptom Indices Over Time - IPSS |
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Inclusion criteria:
Histologically confirmed adenocarcinoma of the prostate
Demonstrates intra-prostatic metabolite abnormalities, consistent with adenocarcinoma of the prostate (i.e., ≥ 3 voxels with magnetic resonance spectroscopy imaging [MRSI] scores 4-5) by baseline MRI and MRSI
Has symptomatic benign prostatic hypertrophy and is currently undergoing watchful waiting OR opting to undergo permanent seed implant (i.e., brachytherapy), but requires neoadjuvant androgen suppression for prostate shrinkage
No regional lymph node involvement
No evidence of distant metastases
Zubrod performance status 0-1
Able to swallow and retain oral medications
Exclusion Criteria:
Other prior or concurrent invasive cancer, other than localized basal cell or squamous cell carcinoma of the skin
Contraindications to MRI/MRSI, including any of the following:
Unstable serious co-morbidities including, but not limited to, myocardial infarction, coronary artery syndrome, cardiac arrhythmias, symptomatic congestive heart failure, or cerebrovascular accident
Major medical or psychiatric illness that, in the investigator's opinion, would preclude the completion of treatment and interfere with follow up
Known hypersensitivity to any 5α-reductase inhibitor or drug chemically related to the study drug
Prior radical surgery (prostatectomy) or cryosurgery for prostate cancer
Prior pelvic irradiation, prostate brachytherapy, or bilateral orchiectomy
Prior or concurrent cytotoxic chemotherapy for prostate cancer
Prior hormonal therapy, such as luteinizing hormone-releasing hormone agonists (e.g., goserelin or leuprolide acetate), antiandrogens (e.g., flutamide or bicalutamide), or estrogens (e.g., diethylstilbestrol)
Prior or concurrent finasteride, dutasteride, other drugs with known antiandrogenic properties (e.g., spironolactone or progestational agents), or any dietary or herbal supplement (e.g., selenium, vitamin E, saw palmetto, or PC-SPES)
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| Name | Affiliation | Role |
|---|---|---|
| Mack Roach, MD | University of California, San Francisco | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco | California | 94115 | United States |
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Patients were recruited from June 2005 to June 2008 from untreated patients seen at the University of California San Francisco
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| ID | Title | Description |
|---|---|---|
| FG000 | Dutasteride | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months dutasteride : 6 months of dutasteride 3.5 mg daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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IPSS (The International Prostate Symptom Score) is a symptom index based on seven questions concerning urinary symptoms (1 Incomplete emptying, 2 Frequency, 3 Intermittency, 4 Urgency, 5 Weak Stream, 6 Straining, 7 Nocturia) for which the patient chooses one out of six answers indicating increasing severity of the particular symptom, ranging from 0 (Not at all) to 5(Almost always). The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Mild (symptom score less than of equal to 7); Moderate (symptom score range 8-19); Severe (symptom score range 20-35).
| Baseline, 1, 3, and 6 months |
| Symptom Indices Over Time - IIEF-5 | The International Index of Erectile Function (IIEF-5) is an abridged five-item version of the original IIEF 15-item questionnaire designed to evaluate erectile function, based on a definition arrived at by the National Institutes of Health Consensus Panel. Each of 5 questions about erectile function over the past 6 months is scored by the patient from 1 (severe dysfunction) to 5 (little or no dysfunction). The IIEF-5 is scored from 5 to 25, with lower scores indicating erectile dysfunction: 22-25 = No erectile dysfunction; 17-21 = Mild erectile dysfunction; 12-16 = Mild to moderate erectile dysfunction; 8-11 = Moderate erectile dysfunction; 5-7 = Severe erectile dysfunction | Baseline, 1, 3, and 6 months |
| Health-Related Quality of Life (HRQL) Indices Over Time - FACE | Functional Alterations due to Changes in Elimination (FACE) is a 14-item questionnaire designed to evaluate the effects of changes in urinary and bowel elimination on daily functioning. It is scored out of 56, with higher scores reflecting poorer HRQL. | Baseline, 1, 3, and 6 months |
| Health-Related Quality of Life (HRQL) Indices Over Time - SQLI | The Spitzer Quality of Life Index (SQLI) is a validated five-item questionnaire evaluating global HRQL. Activity, daily living, health, support of family and friends, and outlook are each rated on a 3-point scale (0 to 2), with total score ranging from 0-10, with lower score indicating poorer HRQL. | Baseline, 1, 3, and 6 months |
| Total PSA Over Time | Baseline, 1, 3, and 6 months |
| Dihydrotestosterone (DHT) Over Time | Baseline, 1, 3, and 6 months |
| Testosterone Over Time | Baseline, 1, 3, and 6 months |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Dutasteride | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months dutasteride : 6 months of dutasteride 3.5 mg daily |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Full Range | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Clinical Stage | In the TNM system, T refers to the primary prostate tumor, N refers to the status of the lymph nodes near to the prostate, and M refers to the degree to which prostate cancer has traveled out of the immediate area of the prostate to other organs of the body (metastases). T1c = a positive prostate specific antigen (PSA) test but no other clinical sign of the disease (i.e., no abnormality felt on digital rectal examination or visible on any form of imaging test). T2a = tumor is palpable or visible on imaging (ultrasound or MRI) in not more than half of one side (one lobe) of the prostate. | Number | Participants |
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| Total PSA | The prostate-specific antigen (PSA) test measures the blood level of PSA, a protein that is produced by the prostate gland. | Median | Full Range | ng/mL |
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| Prostate volume | To assess prostate volume, regions of interest were manually drawn around the prostate across its full three-dimensional extent on the T2-weighted MR images; at subsequent timepoints, prostate volume was assessed as a percentage of the baseline value. | Mean | Full Range | mL |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Extent of Cancer | Proportion of voxels consistent with prostate cancer as measured by magnetic resonance spectroscopy imaging (MRSI). MRSI spectra were examined and scored as healthy or cancerous. The change in cancerous volumes over time was evaluated. Because a significant decrease in citrate and polyamines on MRSI spectra was noted at 1 month compared with baseline, healthy tissue appeared to be more like cancer and thus created a false impression that the cancer had grown after 1 month. To reduce this bias, primary comparisons were made between the 1-month and 6-month scans. | One participant withdrew from the study | Posted | Number | participants | 1 month, 6 months |
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| Secondary | Adverse Events Indicative of Safety of Dutasteride | Toxicities from Dutasteride were recorded at each study visit and assessed by NCI-CTCAE v3.0. | Posted | Number | adverse events | Baseline, 1, 3, and 6 months |
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| Secondary | Symptom Indices Over Time - IPSS | IPSS (The International Prostate Symptom Score) is a symptom index based on seven questions concerning urinary symptoms (1 Incomplete emptying, 2 Frequency, 3 Intermittency, 4 Urgency, 5 Weak Stream, 6 Straining, 7 Nocturia) for which the patient chooses one out of six answers indicating increasing severity of the particular symptom, ranging from 0 (Not at all) to 5(Almost always). The total score can therefore range from 0 to 35 (asymptomatic to very symptomatic). Mild (symptom score less than of equal to 7); Moderate (symptom score range 8-19); Severe (symptom score range 20-35). | Because one participant withdrew from the study prior to 6-months, n=9 at 6 months. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 1, 3, and 6 months |
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| Secondary | Symptom Indices Over Time - IIEF-5 | The International Index of Erectile Function (IIEF-5) is an abridged five-item version of the original IIEF 15-item questionnaire designed to evaluate erectile function, based on a definition arrived at by the National Institutes of Health Consensus Panel. Each of 5 questions about erectile function over the past 6 months is scored by the patient from 1 (severe dysfunction) to 5 (little or no dysfunction). The IIEF-5 is scored from 5 to 25, with lower scores indicating erectile dysfunction: 22-25 = No erectile dysfunction; 17-21 = Mild erectile dysfunction; 12-16 = Mild to moderate erectile dysfunction; 8-11 = Moderate erectile dysfunction; 5-7 = Severe erectile dysfunction | One participant withdrew from the study prior to the 6 month timepoint; thus n=9 at 6 months. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 1, 3, and 6 months |
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| Secondary | Health-Related Quality of Life (HRQL) Indices Over Time - FACE | Functional Alterations due to Changes in Elimination (FACE) is a 14-item questionnaire designed to evaluate the effects of changes in urinary and bowel elimination on daily functioning. It is scored out of 56, with higher scores reflecting poorer HRQL. | One participant withdrew from the study prior to the 6 month timepoint; thus n=9 at 6 months. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 1, 3, and 6 months |
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| Secondary | Health-Related Quality of Life (HRQL) Indices Over Time - SQLI | The Spitzer Quality of Life Index (SQLI) is a validated five-item questionnaire evaluating global HRQL. Activity, daily living, health, support of family and friends, and outlook are each rated on a 3-point scale (0 to 2), with total score ranging from 0-10, with lower score indicating poorer HRQL. | One participant withdrew from the study prior to 6 months; thus, n=9 at 6 months. | Posted | Mean | Standard Deviation | units on a scale | Baseline, 1, 3, and 6 months |
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| Secondary | Total PSA Over Time | Because one participant withdrew from the study prior to 6-months, n=9 for the 6-month Mean(SD) levels. | Posted | Mean | Standard Deviation | ng/mL | Baseline, 1, 3, and 6 months |
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| Secondary | Dihydrotestosterone (DHT) Over Time | Because one participant withdrew from the study prior to 6-months, n=9 at 6 months. | Posted | Mean | Standard Deviation | ng/dL | Baseline, 1, 3, and 6 months |
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| Secondary | Testosterone Over Time | Because one participant withdrew from the study prior to 6-months, n=9 at 6 months. | Posted | Mean | Standard Deviation | ng/dL | Baseline, 1, 3, and 6 months |
|
6 months
Toxicities from dutasteride were recorded at each follow-up visit using the National Cancer Institute's Common Terminology Criteria for Adverse Events toxicity scale version 3.0
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dutasteride | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months dutasteride: 6 months of dutasteride 3.5 mg daily | 0 | 10 | 4 | 10 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Rash | Skin and subcutaneous tissue disorders | CTCAE | Systematic Assessment |
| |
| Decreased ejaculate volume | Reproductive system and breast disorders | CTCAE | Systematic Assessment |
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The inclusion of only men with low volume disease may have limited our ability to accurately assess response rates after dutasteride due to the background effects on normal prostate metabolism.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mack Roach, MD | University of California San Francisco | 415-353-9855 | tdiep@radonc.ucsf.edu |
| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D011471 | Prostatic Neoplasms |
| D011470 | Prostatic Hyperplasia |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
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| ID | Term |
|---|---|
| D000068538 | Dutasteride |
| ID | Term |
|---|---|
| D001378 | Azasteroids |
| D013260 | Steroids, Heterocyclic |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Denominators | Categories |
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| OG003 | Dutasteride - 6 Months | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months. IPSS was assessed at 6 months. |
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Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months. IIEF-5 was assessed at 3 months. |
| OG003 | Dutasteride - 6 Months | Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months. IIEF-5 was assessed at 6 months. |
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Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months. FACE was assessed at 6 months. |
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| Dutasteride - 6 Months |
Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months. SQLI was assessed at 6 months. |
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