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Focal Therapy for Prostate Cancer Using HIFU (INDEX)

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ClinicalTrials.gov Identifier: NCT01194648
Recruitment Status : Recruiting
First Posted : September 3, 2010
Last Update Posted : April 20, 2018
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:
RATIONALE: Prospective trials using hemi-ablation with high intensity focused ultrasound (HIFU) (Sonablate 500) have demonstrated feasibility, safety, and encouraging functional outcomes and early cancer control with 90% of men achieving trifecta status (no erectile dysfunction, leak-free pad-free continence, cancer control). However, these trials have involved small numbers of patients with men selected for good baseline function. A multi-centre prospective trial within a larger cohort of men that better represents the patient population with prostate cancer (external validity) is required.

Condition or disease Intervention/treatment Phase
Male Erectile Disorder Prostate Cancer Therapy-related Toxicity Urinary Incontinence Other: questionnaire administration Procedure: assessment of therapy complications Procedure: high-intensity focused ultrasound ablation Procedure: multiparametric magnetic resonance imaging Procedure: quality-of-life assessment Procedure: transperineal prostate biopsy Procedure: transrectal prostate biopsy Not Applicable

Detailed Description:

Verification of a new therapy as favourable, or equivalent, in outcome to 'standard' care is ideally sought through comparison with another matched control group. Randomised controlled trials (RCTs) offer the best method for minimising systematic bias and revealing the true effect of an intervention or drug. However, RCTs involving treatments of localised prostate cancer have had a historically poor patient uptake, as the reference 'gold' standard of care is not known. In addition, RCTs are expensive to run and involve huge infra-structural support. A number of trials in the USA have been forced to close due to lack of recruitment. The ProStart trial in the UK has also had to close for the same reason. It has been acknowledged by the Food and Drug Agency in the USA that comparative randomized trials will be problematic in this area due to lack of physician and patient equipoise. A randomized trial may be feasible if a pragmatic design is adopted but prior to acceptance of such a design, the number of centres with expertise in this complex intervention (mp-MRI, TTPM, focal HIFU) will need to be increased.

Observational studies are a commonly used alternative to ascertain the effectiveness of a treatment. They are used to observe a treatment effect in a selected group of patients who are presumed to derive benefit from the treatment given. Although methodologically not as robust, and therefore prone to bias, they have some benefits over RCTs. The principal ones are those of enhanced external validity (many patients do not wished to be randomised and therefore refuse participation), and more rapid accrual compared to a randomised design. For this reasons, a single arm medium term follow-up cohort intervention study has been designed. At the time of writing the safety and tolerability aspects of focal therapy by HIFU are known as a result of the Phase I/II studies carried out at UCLH. The results have been presented and exist in the public domain in abstract form but have not yet been published (presented in tables above). These early studies were powered to detect a change in the proportion of men who could obtain an erection sufficient for penetration compared to their status prior to their treatment. The very low event rate for both erectile dysfunction and incontinence indicates that the 'proof of concept' has been demonstrated for focal therapy. Moreover, we can be relatively confident that, in expert hands, focal HIFU is safe. Therefore, a multi-centre study is now required involving a larger group of patients for the following reasons:

  1. To evaluate medium term cancer control using histological parameters. Stage two of INDEX will evaluate conversion to radical and systemic therapies and link men to national databases to determine survival in 5 and 10 years.
  2. To confirm that focal therapy can lead to low rates of genitourinary and rectal toxicity and minimal impact on quality of life within a large and more representative cohort of patients (greater precision around outcome measures).
  3. To demonstrate that the skills (characterization through template prostate mapping and MRI as well as the treatment related skills) acquired by the team at UCLH are indeed transferable to other providers.
  4. To calculate costs of care and to model potential cost-effectiveness in comparison to alternative therapies. If this single arm intervention study demonstrates acceptable outcomes to support the findings of the Phase I/II studies, it is anticipated that this preliminary study will lead onto a Phase III evaluation of focal therapy, prior to more widespread use of this technology.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 354 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Multi-Centre Prospective Single Arm Intervention Trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center Prospective Single Arm Intervention Trial Evaluating Focal Therapy Using High Intensity Focused Ultrasound (Sonablate 500) for Localized Prostate Cancer
Actual Study Start Date : June 29, 2011
Estimated Primary Completion Date : December 2028
Estimated Study Completion Date : June 2029

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
High Intensity Focused Ultrasound
HIFU, the Intervention
Other: questionnaire administration Procedure: assessment of therapy complications Procedure: high-intensity focused ultrasound ablation Procedure: multiparametric magnetic resonance imaging Procedure: quality-of-life assessment Procedure: transperineal prostate biopsy Procedure: transrectal prostate biopsy



Primary Outcome Measures :
  1. Conversion to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer [ Time Frame: 5 years ]
    To determine the proportion of men converting to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer following focal therapy for localised prostate cancer using HIFU

  2. Conversion to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer [ Time Frame: 10 years ]
    To determine the proportion of men converting to radical therapy and/or requiring systemic therapy and/or developing metastases and/or dying of prostate cancer following focal therapy for localised prostate cancer using HIFU


Secondary Outcome Measures :
  1. rate of erectile dysfunction [ Time Frame: 12 months ]
    The presence of severe erectile dysfunction at 12 months, as measured by the IIEF-5 questionnaire with or without the use of phosphodiesterase-5 inhibitors, in those with absence of severe erectile dysfunction at baseline

  2. rate of erectile dysfunction [ Time Frame: 24 months ]
    The presence of severe erectile dysfunction at 24 months, as measured by the IIEF-5 questionnaire with or without the use of phosphodiesterase-5 inhibitors, in those with absence of severe erectile dysfunction at baseline

  3. time to return of erectile function [ Time Frame: 24 months ]
    Time to return of erectile function (absence of severe ED on IIEF-15 questionnaire)

  4. rate of urinary incontinence (pad free, leak free and pad-free alone) [ Time Frame: 12 months ]
    Presence of urinary incontinence (any pad usage plus any leakage of urine) as determined by the UCLA-EPIC urinary continence questionnaire, at 12 months, in those men with no urinary incontinence at baseline

  5. rate of urinary incontinence (pad free, leak free and pad-free alone) [ Time Frame: 24 months ]
    Presence of urinary incontinence (any pad usage plus any leakage of urine) as determined by the UCLA-EPIC urinary continence questionnaire, at 24 months, in those men with no urinary incontinence at baseline

  6. time to return of continence (pad free, leak free and pad-free alone) [ Time Frame: 24 months ]
    Time to return of urinary continence (as determined by UCLA-EPIC Urinary domain questionnaire)

  7. rate of loss of ejaculation [ Time Frame: 24 months ]
    rate of loss of ejaculation (as determined by IIEF-15 questionnaire)

  8. rate of loss of orgasm [ Time Frame: 24 months ]
    rate of loss of orgasm (as determined by IIEF-15 questionnaire)

  9. rate of pain during intercourse [ Time Frame: 24 months ]
    rate of pain during intercourse (as determined by IIEF-15 questionnaire)

  10. number of men using phosphodiesterase-5 inhibitors to maintain erectile function [ Time Frame: 24 months ]
    Need for phosphodiesterase-5 inhibitors to maintain erectile function sufficient for penetration up to 24 months

  11. rate of lower urinary tract symptoms [ Time Frame: 24 months ]
    Grading of lower urinary tract symptoms as determined by IPSS scores

  12. rate of bowel toxicity [ Time Frame: 24 months ]
    UCLA-EPIC Bowel Function Questionnaire

  13. anxiety levels [ Time Frame: 24 months ]
    EQ-5D Quality of Life Questionnaire

  14. general health related quality of life [ Time Frame: 24 months ]
    General and prostate health related quality of life measured using EQ-5D Quality of Life questionnaire

  15. proportion of men achieving trifecta status at 12 months [ Time Frame: 12months ]
    Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 12 months in those men with good baseline function

  16. proportion of men achieving trifecta status at 24 months [ Time Frame: 24 months ]
    Achievement of trifecta status (no severe ED, pad-free leak-free continence, cancer control with absence of clinically significant cancer) at 24 months in those men with good baseline function

  17. rate of secondary prostate cancer intervention (prostatectomy, radiotherapy, androgen ablation, whole-gland HIFU or cryosurgery) [ Time Frame: 24 months ]
    rate of secondary prostate cancer intervention (prostatectomy, radiotherapy, androgen ablation, whole-gland HIFU or cryosurgery)

  18. risk factors for failure defined as a) presence of any cancer and b) clinically significant cancer at study end [ Time Frame: 24 months ]
    risk factors for failure defined as a) presence of any cancer and b) clinically significant

  19. biochemical (PSA) kinetics including determining the optimal biochemical definition of failure [ Time Frame: 24 months ]
    biochemical (PSA) kinetics including determining the optimal biochemical definition of

  20. describe composite outcomes of failure [ Time Frame: 24 months ]
    describe composite outcomes of failure

  21. Cost-effectiveness [ Time Frame: 5years ]
    To determine the costs of treatment and model potential cost effectiveness using comparative cancer control and functional outcomes at 5 years compared to other cohort trials involving the management of localized prostate cancer

  22. Cost-effectiveness [ Time Frame: 10 years ]
    To determine the costs of treatment and model potential cost effectiveness using comparative cancer control and functional outcomes at 10 years compared to other cohort trials involving the management of localized prostate cancer



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Ages Eligible for Study:   up to 90 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  1. Histologically proven prostate cancer on trans-rectal or transperineal template prostate biopsies.
  2. Prostate biopsy (either TRUS or MRI Targeted or Template):

    • TRUS biopsy: up to burden bilateral disease with maximum 3mm one biopsy on non-dominant side is allowable.
    • MRI targeted and/or Template biopsy within 12 months of entry showing:
    • unilateral disease minimum 3mm of Gleason 3+3 or any Gleason 3+4 or 4+3 but not exceeding Gleason 4+3 overall OR
    • bilateral disease presence of clinically significant cancer on only one side (as determined by histological rules described above) Gleason ≤7 which is concordant with the MRI findings.
  3. Stage T1-T2cN0M0 disease, as determined by local guidelines (radiological T3a permitted).
  4. Serum PSA </=20ng/ml
  5. Life expectancy of >/=10 years.
  6. Signed informed consent by patient.
  7. An understanding of the English language sufficient to understand

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01194648


Locations
United Kingdom
University College London Recruiting
London, England, United Kingdom, WC1E 6BT
Contact: SITU Trials Unit    +44207 679 9280    situ.index@ucl.ac.uk   
Sponsors and Collaborators
University College, London
Investigators
Study Chair: Mark Emberton, MD, FRCS, MBBS University College, London
Study Chair: Hashim Uddinn Ahmed, MD, FRCS Imperial College London

Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT01194648     History of Changes
Other Study ID Numbers: CDR0000684020
9945 ( Other Grant/Funding Number: NIHR - CPMS ID )
First Posted: September 3, 2010    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University College, London:
urinary incontinence
male erectile disorder
therapy-related toxicity
stage I prostate cancer
stage IIB prostate cancer
stage IIA prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Urinary Incontinence
Enuresis
Erectile Dysfunction
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Urination Disorders
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Behavioral Symptoms
Elimination Disorders
Mental Disorders
Sexual Dysfunction, Physiological
Sexual Dysfunctions, Psychological