Dutasteride in Treating Patients With Prostate Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01193855
First received: September 1, 2010
Last updated: August 23, 2013
Last verified: August 2011
  Purpose

RATIONALE: Dutasteride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This randomized phase II trial is studying how well giving dutasteride works in treating patients with prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: dutasteride
Drug: gadolinium-chelate
Other: active surveillance
Procedure: diffusion-weighted magnetic resonance imaging
Procedure: functional magnetic resonance imaging
Procedure: prostate biopsy
Procedure: ultrasound imaging
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Single Site, Phase II, Double Blind, Randomized, Placebo Controlled Study of the Effect of Dutasteride (Avodart) 0.5mg on the Volume and Characteristics of Prostate Cancer, as Assessed by Multifunctional Magnetic Resonance Imaging (MRI) With Lower Risk Prostate Cancer Suitable for Active Surveillance. (MAPPED TRIAL)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • The change in volume of foci of prostate cancer (PC) as assessed by T2-weighted (T2w) MRI between baseline and 6 months [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The change in volume of PC as determined by gadolinium-enhanced (GE) MRI and diffusion-weighted (DW) MRI at 6 months [ Designated as safety issue: No ]
  • The change in volume of PC as determined by T2w MRI, GE MRI, and DW MRI at 3 months [ Designated as safety issue: No ]
  • The changes in MR characteristics of PC (perfusion, cell density) between baseline and 6 months [ Designated as safety issue: No ]
  • The change in volume of PC as assessed by HistoScan transrectal ultrasound (TRUS) between baseline and 6 months [ Designated as safety issue: No ]
  • The association between the measured PC volumes on MRI with the measured PC volumes on TRUS at baseline and 6 months [ Designated as safety issue: No ]
  • The association between the measured changes in PC volume using MRI vs TRUS at baseline and 6 months [ Designated as safety issue: No ]
  • The association of PC volume change with qualitative changes seen on TRUS between baseline and 6 months [ Designated as safety issue: No ]
  • The association between MR changes in volume and characteristics with histological features as seen on 6-month biopsy (Gleason score and sum, number of cores involved, cancer core length) [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: June 2010
Estimated Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the change in volume of foci of prostate cancer as assessed by T2-weighted MRI, following exposure to dutasteride (Avodart) 0.5 mg daily for six months.

Secondary

  • To determine the change in volume of prostate cancer as determined by gadolinium-enhanced MRI and diffusion-weighted MRI after 6 months of dutasteride 0.5 mg compared to placebo.
  • To determine the change in volume of prostate cancer as determined by T2-weighted MRI, gadolinium-enhanced MRI, and diffusion-weighted MRI after 3 months of dutasteride compared to placebo.
  • To determine the changes in MR characteristics of prostate cancer (perfusion, cell density) between baseline and six months in patients on dutasteride compared to placebo.
  • To determine the change in volume of prostate cancer as assessed by HistoScan transrectal ultrasound between baseline and six months, in patients on dutasteride compared to placebo.
  • To determine the association between the measured prostate cancer volumes on MRI with the measured prostate cancer volumes on HistoScan at baseline and six months in patients on dutasteride compared to placebo.
  • To determine the association between the measured changes in prostate cancer volume using MRI, and the measured changes in prostate cancer volume using HistoScan transrectal ultrasound, at baseline and at six months, in patients on dutasteride compared to placebo.
  • To correlate changes in tumor volume and characteristics seen on MRI with changes seen on HistoScan between baseline and six months in patients on dutasteride compared to placebo.
  • To correlate change in tumor volume and characteristics seen on MRI with histological features as seen on 6-month biopsy (Gleason score and sum, number of cores involved, cancer core length) in patients on dutasteride compared to placebo.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral dutasteride once daily for 6 months. Treatment continues in the absence of unacceptable toxicity.
  • Arm II: Patients receive oral placebo once daily for 6 months. Treatment continues in the absence of unacceptable toxicity.

Patients undergo a multi-sequence MRI at baseline, 3 months, and 6 months and HistoScan transrectal ultrasound at baseline and 6 months. Patients may also undergo a targeted biopsy of the prostate (standard transrectal biopsy plus ultrasound-guided targeting of lesions seen on MRI) at 6 months.

  Eligibility

Ages Eligible for Study:   up to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed prostate cancer, meeting all of the following criteria:

    • Prostate-specific antigen (PSA) < 10.0 ng/mL
    • T1c-T2a disease
    • Gleason sum of 6 or 7 (secondary pattern 4 only)
  • Patients with low risk disease must meet the following criteria:

    • Gleason pattern 3 + 3
    • PSA < 10.0 ng/mL
    • Clinical T2a disease
  • Patients with Gleason secondary pattern 4 (i.e., Gleason Pattern 3 + 4) are eligible but must not have a primary pattern 4, PSA > 10 ng/mL, or clinical T2b disease
  • Measurable disease on MRI of at least 0.2 cc, based on planimetry volume
  • Biopsy-proven disease within 2 years of screening visit

    • No biopsy artifact on MRI scan (minimum 12-week interval between biopsy and baseline MRI)
  • Eligible for active surveillance according to the criteria set out by the National Institute for Health and Clinical Excellence

PATIENT CHARACTERISTICS:

  • ALT and AST ≤ 2 times the upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min
  • Able to swallow and retain oral medication
  • Able and willing to participate in the study for its duration
  • Able to read and write (health-outcomes questionnaires are written)
  • Able to understand instructions related to study procedures and give written informed consent
  • No history of another malignancy within five years that could affect the diagnosis of prostate cancer
  • No history or current evidence of drug or alcohol abuse within the last 12 months that might confound the results of the study or pose additional risk to the patient
  • No known hypersensitivity to any 5α-reductase inhibitor or to any drug chemically related to dutasteride
  • No contraindication for undergoing gadolinium-enhanced MRI, including any of the following:

    • Inability to see tumor focus of ≥ 0.2 cc on T2 sequences
    • Previous allergic reaction to gadolinium
    • Serum creatinine > ULN
    • Incompatible pacemaker
    • Metal fragments in eyes
    • Hip replacements that give artifact with prostate/pelvis views
    • Any artifact or condition that reduces image quality of MRI (e.g., inability to keep still)
  • No unstable serious co-existing medical condition(s) including, but not limited, to any of the following:

    • Myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to screening visit
    • Uncontrolled diabetes
    • Peptic ulcer disease uncontrolled by medical management

PRIOR CONCURRENT THERAPY:

  • No prior radiotherapy (external-beam or brachytherapy), high-intensity focused ultrasound (HIFU), or photodynamic therapy (PDT)
  • No prior chemotherapy
  • At least 3 months since prior and no concurrent prostatic surgery, including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation
  • No prior oral glucocorticoids

    • Glucocorticoids, except inhaled or topical, are not permitted within 3 months prior to visit one
  • No prior GnRH analogues (e.g., leuprolide, goserelin)
  • No prior or concurrent hormonal treatment (e.g., megestrol, medroxyprogesterone, cyproterone, DES) of prostate cancer
  • No current and/or prior use of the following medications:

    • Finasteride (Proscar, Propecia), or dutasteride (GI198745, AVODART) exposure within 12 months prior to study entry
    • Any other investigational 5α-reductase inhibitors within the past 12 months
    • Anabolic steroids within the past 6 months
    • Drugs with antiandrogenic properties within the past 6 months (e.g., spironolactone, flutamide, bicalutamide, cimetidine, ketoconazole, progestational agents)

      • The use of cimetidine is permitted prior to study entry
      • The use of topical ketoconazole is permitted prior to and during the study
  • No participation in another investigational or marketed drug trial within the 30 days prior to the first dose of study drug or anytime during the study period
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01193855

Locations
United Kingdom
University College of London Hospitals Recruiting
London, England, United Kingdom, W1T 7NF
Contact: Contact Person    44-207-380-9194    markemberton1@btinternet.com   
Sponsors and Collaborators
University College London Hospitals
Investigators
Principal Investigator: Mark Emberton, MD, FRCS, MBBS University College London Hospitals
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01193855     History of Changes
Other Study ID Numbers: CDR0000684018, UCL-09-0221, EUDRACT-2009-012405-18, EU-21067
Study First Received: September 1, 2010
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IIB prostate cancer
stage IIA prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Dutasteride
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Urological Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 02, 2014