MRI and Magnetic Resonance Spectroscopy Imaging in Patients Receiving Dutasteride for Benign Prostatic Hypertrophy and Low-Risk Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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OBJECTIVES: Primary To determine whether there is a decrease in the extent of prostate cancer as measured by endorectal MRI and magnetic resonance spectroscopy imaging in patients with symptomatic benign prostatic hypertrophy and low-risk prostate cancer treated with dutasteride for 6 months. Secondary To monitor the effects of dutasteride on serum testosterone, dihydrotestosterone, and free and total prostate-specific antigen (PSA). To monitor the effects of dutasteride on symptom and quality-of-life indices. 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.

Official Title
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A Pilot Study of MRI and Spectroscopy Imaging Changes With 6-months of Dutasteride in Patients With Symptomatic Benign Prostatic Hypertrophy and Low-risk Prostate Cancer on Watchful Waiting or Requiring Neoadjuvant Androgen Suppression Prior to Prostate Brachytherapy

Conditions
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Nonmalignant Neoplasm, Prostate Cancer

Intervention / Treatment
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* Drug: dutasteride


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Histologically confirmed adenocarcinoma of the prostate Clinical stage T1b, T1c, or T2a disease Gleason score ≤ 6 Maximal prostate-specific antigen (PSA) < 10 ng/mL 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: Prostate biopsy (within the past 8 weeks) and any continued post-biopsy bleeding Rectal bleeding Anal fissures Rectal surgery (end-to-end anastomosis) Inflammatory bowel disease Prior radical prostatectomy Hip replacement Certain types of penile implants Vascular clips Known anaphylactic reaction to latex compounds Anticoagulant drugs Severe claustrophobia Cardiac pacemaker Metal in eye Any other metallic or foreign object in the body 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)
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dutasteride<br>Dutasteride was administered at a dose of 3.5 mg as an oral soft gelatin capsule once daily for 6 months | Drug: dutasteride<br>* 6 months of dutasteride 3.5 mg daily<br>* Other names: Avodart;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IIB prostate cancer, stage IIA prostate cancer, benign prostatic hyperplasia