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Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU (High Intensity Focused Ultrasound) Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer (HIFUSA)

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ClinicalTrials.gov Identifier: NCT03531099
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : September 19, 2018
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:

The percentage of malignant prostate tumors detected very early is constantly increasing and the number of well differentiated tumors, with small volume and low risk of progression increases. When a tumor of this type is identified, radical prostatectomy remains the reference treatment, but this treatment is not without side effects. Active surveillance is a strategy which aims at detecting an early development of the cancerous disease in order to propose curative treatment in a timely manner and thus improve specific survival. Patients are therefore re-evaluated each year by rectal examination, PSA (Prostate-Specific Antigen) assay. Active surveillance remains difficult to manage psychologically for both the patient and the practitioner, because of the lack of treatment on the one hand and a rate of non-curable cancers close to 50% when signs of progression trigger a radical treatment.

The aim of the focal treatment HIFU (High Intensity Focused Ultrasound) is to destroy the cancer without causing side effects in contrast to radical treatments. It is in this sense that it is positioned both as an alternative to radical surgery and as an alternative to active surveillance.


Condition or disease Intervention/treatment Phase
Prostate Cancer Procedure: treatment with focal HIFU Biological: PSA dosage Device: MRI Other: Questionnaires Procedure: Prostatic biopsies Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3, Multicenter, Randomized Study, Evaluating the Efficacy and Tolerability of Focused HIFU Therapy Compared to Active Surveillance in Patients With Significant Low Risk Prostate Cancer
Estimated Study Start Date : September 18, 2018
Estimated Primary Completion Date : July 1, 2023
Estimated Study Completion Date : July 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: HIFU treatment

65 patients will receive the immediate treatment with focal HIFU in order to destroy the cancer without causing side effects. HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

Procedure: treatment with focal HIFU
HIFU treatment will be conducted with the Focal One® device. The treatment area will be defined using MRI data and 3D biopsies. A safety distance of at least 9 mm will be defined around the tumor. An intraoperative contrast echocardiographic control will be performed to evaluate the necrotic area. If necessary, additional HIFU lesions will be performed during the same session. In case of residual tumor demonstrated during control biopsies, additional treatment of this tumor with focal HIFU may be proposed.

Biological: PSA dosage
PSA dosage will be regularly performed during patient follow up thanks to blood sampling.

Device: MRI
MRI exam will be regularly performed during patient follow up.

Other: Questionnaires
Patients will have to complete five questionnaires during their follow up : QLQ-C30 (Quality of Life questionnaire), EPIC-26 (The Expanded Prostate Cancer Index Composite), IPSS (International Prostate Score Symptom), IIEF-5 (The International Index of Erectile Function), STAI-YB (State-Trait Anxiety Inventory)

Procedure: Prostatic biopsies
Prostatic biopsies will be regularly performed during patient follow up.

Active Comparator: Active surveillance

65 patients will be randomized to active surveillance and will have exactly the same follow-up as treated patients excepting the HIFU treatment.

Active surveillance is a therapeutic option that shifts the eventual moment of curative treatment while remaining within a window of curability of the disease.

Patients randomized in this arm will also have PSA dosage, MRI exam, questionnaires and prostatic biopsies during their follow up.

Biological: PSA dosage
PSA dosage will be regularly performed during patient follow up thanks to blood sampling.

Device: MRI
MRI exam will be regularly performed during patient follow up.

Other: Questionnaires
Patients will have to complete five questionnaires during their follow up : QLQ-C30 (Quality of Life questionnaire), EPIC-26 (The Expanded Prostate Cancer Index Composite), IPSS (International Prostate Score Symptom), IIEF-5 (The International Index of Erectile Function), STAI-YB (State-Trait Anxiety Inventory)

Procedure: Prostatic biopsies
Prostatic biopsies will be regularly performed during patient follow up.




Primary Outcome Measures :
  1. patient proportion who needed to seek radical treatment [ Time Frame: 48 month ]

    The primary endpoint is the comparison between the 2 groups of the proportion of patient converting to a radical treatment at 48 months of follow-up. Conversion to a radical treatment is define as a medical decision based on the following criteria:

    • An increase in Gleason score to a score 7 (3 + 4) with bilateral involvement (Gleason 6 or 7).
    • An increase in the Gleason score to a score 7 (3 + 4) with tumor whose location is not compatible with a focal treatment (impossibility to apply safety margins of 9mm).
    • An increase in Gleason score to a score of 7 (4 + 3) or higher.
    • Risk of lymph node invasion> 5% (calculated with the MSKCC nomogram)
    • An extension of the tumor beyond the prostatic capsule (MRI and / or biopsies).
    • Appearance of pelvic ganglion metastases.


Secondary Outcome Measures :
  1. proportion of patients needing additional treatment [ Time Frame: 24 months ]
    The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 24 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

  2. proportion of patients needing additional treatment [ Time Frame: 48 months ]
    The objective is to compare between the 2 groups the proportion of patients needing additional treatment (focal or radical) at 48 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, focal treatment for patients in the active surveillance group or additional treatment for patients in the treatment group.

  3. rate of positive biopsies [ Time Frame: 24 months ]
    The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the oncological evolution at 24 months.

  4. rate of positive biopsies [ Time Frame: 48 months ]
    The rate of positive biopsies in the untreated lobe and treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

  5. clinically significant cancer rate [ Time Frame: 24 months ]
    The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 24 months.

  6. clinically significant cancer rate [ Time Frame: 48 months ]
    The clinically significant cancer rate (Gleason 7 or invasion of more than 3 biopsies or invasion> 3 mm regardless of Gleason) in the untreated lobe and the treated lobe will be measured and will be used to evaluate the oncological evolution at 48 months.

  7. Gleason score [ Time Frame: 24 months ]
    Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 24 months.

  8. Gleason score [ Time Frame: 48 months ]
    Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the oncological evolution at 48 months.

  9. Appearance of another cancerous focus in the other half of the prostate [ Time Frame: 24 months ]
    Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 24 months.

  10. Appearance of another cancerous focus in the other half of the prostate [ Time Frame: 48 months ]
    Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the oncological evolution at 48 months.

  11. Appearance of metastases [ Time Frame: 24 months ]
    Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 24 months.

  12. Appearance of metastases [ Time Frame: 48 months ]
    Appearance of metastases (lymph node or bone) will be supervised and will be used to evaluate the oncological evolution at 48 months.

  13. Appearance of an extra capsular extension [ Time Frame: 24 months ]
    Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 24 months.

  14. Appearance of an extra capsular extension [ Time Frame: 48 months ]
    Appearance of an extra capsular extension will be supervised and will be used to evaluate the oncological evolution at 48 months.

  15. Overall survival [ Time Frame: 48 months ]
    Overall survival at 48 months will be measured from the date of inclusion to the date of death, all causes of death combined or the date of last new or point date to 48 months.

  16. Prostate cancer specific survival [ Time Frame: 48 months ]
    Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of death related to prostate cancer or the date of last new or point date to 48 months

  17. Recurrence free survival [ Time Frame: 48 months ]
    Prostate cancer specific survival at 48 months will be measured from the date of inclusion to the date of first metastasis , or the date of last new or point date to 48 months

  18. Proportion of serious adverse effect [ Time Frame: 48 months ]
    comparison between the 2 groups of the proportion of serious adverse effect at 48 months

  19. Quality of life score [ Time Frame: over the 48 months ]
    quality of life will be compared between the two groups and assessed using the QLQC30 questionnaire

  20. EPIC-26 score [ Time Frame: over the 48 months ]
    urinary function will be compared between the two groups and assessed using the EPIC-26 questionnaire.

  21. IPSS score [ Time Frame: over the 48 months ]
    urinary function will be compared between the two groups and assessed using the IPSS questionnaire.

  22. IIEF-5 score [ Time Frame: over the 48 months ]
    Sexual function will be compared between the two groups and assessed using the IIEF-5 questionnaire

  23. STAi-YB score [ Time Frame: Over the 48 months ]
    Anxiety will be compared between the two groups and assessed using the STAi-YB questionnaire



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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient having been clearly informed of the study and having accepted, with sufficient reflection time, to participate by signing the informed consent form of the study.
  • Age between 50 and 80 years with a life expectancy of more than 5 years. Patients between the ages of 75 and 80 will need to have a lower G8 score.
  • Initial diagnosis of localized prostate cancer (T1 or T2a) with the following characteristics:

    • A multiparametric MRI showing a single invasive tumor focus at most two contiguous sextants confirmed by biopsies (index tumor). Patients with multiple suspected MRI foci may be included if only one of these foci is confirmed by targeted biopsies.
    • The tumor volume on MRI should be> 0.5 cc, ie a tumor ≥10 mm in its longest dimension.
    • A maximum tumor length> 3 mm or at least 3 positive biopsies on all biopsies performed (12 randomized biopsies and 2 biopsies per MRI target guided by fusion software).
    • Gleason 6 score (risk group 1 of the D'Amico classification).
    • Tumor positioned so that a safety distance of at least 9mm can be defined during HIFU-F treatment in prostate tissue around the target.
  • PSA ≤ 10ng / ml.
  • Patient affiliated with health insurance or beneficiary of an equivalent plan.

Exclusion Criteria:

  • Contraindications to treatment with HIFU-F:

    • Tumor not accessible (impossibility to apply a safety margin of 9 mm around the MRI target).
    • Multiple intra prostatic calcifications inducing, on ultrasound, a shadow cone in the prostate preventing the penetration of ultrasound and thus the realization of the treatment.
    • History of pelvic irradiation
    • Presence of an implant (stent, catheter) located less than 1 cm from the treatment area.
    • Fistula of the urinary tract or rectum.
    • Anal or rectal fibrosis, anal or rectal stenosis or other abnormalities making it difficult to insert the Focal One® probe.
    • Anatomical abnormality of the rectum or rectal mucosa.
    • Patient with artificial sphincter, penile prosthesis or intra prostatic implant, eg stent.
    • History of intestinal inflammatory pathology.
    • Uro-genital infection in progress (the infection to be treated before HIFU treatment).
    • Anterior surgery at the level of the anus or rectum making the introduction of the probe impossible.
    • Allergy to latex.
    • Thickness of the rectal wall> 10mm.
  • Patient undergoing treatment for benign prostatic hyperplasia (BPH) with IPSS> 25.
  • Patient with a medical contraindication to Sonovue® injection.
  • Patient with a medical contraindication on MRI.
  • Patient already treated for prostate cancer (hormone therapy, radiotherapy, surgery).
  • History of uncontrolled cancer and / or treated for less than 5 years (with the exception of basal cell skin cancer).
  • History of sclerosis of the bladder neck or urethral stenosis.
  • Patient at risk of bleeding according to medical advice.
  • Patients with unstable neurological pathology.
  • Patient who has been treated for a therapeutic trial within 30 days of enrollment or who wishes to participate in an ongoing study that may interfere with this study.
  • Legal person protected by law.
  • Patient not able to understand the objectives of the study or refusing to comply with postoperative instructions.

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): NCT03531099


Contacts
Contact: Sébastien CROUZET, Pr 04 72 11 03 25 ext +33 sebastien.crouzet@chu-lyon.fr
Contact: Julien BERTHILLER, study manager 04 72 11 80 67 ext +33 julien.berthiller@chu-lyon.fr

Locations
France
Service d'Urologie, Clinique Tivoli Ducos Recruiting
Bordeaux, France, 33000
Contact: Gilles PASTICIER, MD, PhD    05 56 11 61 44 ext +33    gillespasticier@gmail.com   
Service d'Urologie, CHU de Guebwiller Colmar Not yet recruiting
Colmar, France, 68024
Contact: Ludovic OBRINGER, MD, PhD    03 89 12 45 20 ext +33    obringerl@yahoo.fr   
Service d'Urologie CHRU de Lille, Hôpital HURIEZ Not yet recruiting
Lille, France, 59000
Contact: Arnaud VILLIERS, Pr    03 20 44 42 35 ext +33    arnauld.villers@wanadoo.fr   
Service d'Urologie Générale de Santé - Hôpital Privé La Louvière Not yet recruiting
Lille, France, 59000
Contact: Pierre COLIN, MD, PhD    08 26 30 70 00 ext +33    docpierrecolin@gmail.com   
Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot, Recruiting
Lyon, France, 69437
Contact: Sébastien CROUZET, Pr.    04 72 11 03 25 ext +33    sebastien.crouzet@chu-lyon.fr   
Contact: Julien BERTHILLER    04 72 11 80 67 ext +33    julien.berthiller@chu-lyon.fr   
Service d'urologie Assistance Publique - Hôpitaux de Marseille - Hôpital Marseille Nord Not yet recruiting
Marseille, France, 13915
Contact: Harry TOLEDANO, MD, PHD    06 62 69 87 38 ext +33    harry.toledano@ap-hm.fr   
Département d'Urologie, Institut Montsouris Not yet recruiting
Paris, France, 75014
Contact: Eric BARRET, MD, PhD    01 56 61 66 18 ext +33    Eric.Barret@imm.fr   
Clinique Urologique Nantes Atlantis Not yet recruiting
Saint-Herblain, France, 44800
Contact: Eric POTIRON, MD, PhD    02 28 03 04 44 ext +33    potironeric@neuf.fr   
Service d'Urologie, Hôpital Foch Not yet recruiting
Suresnes, France, 92150
Contact: Tarek GHONEIM, MD, PhD    01 46 25 25 25 ext +33    t.ghoneim@hopital-foch.org   
CHU de Toulouse - Hôpital de Rangueil Not yet recruiting
Toulouse, France, 31400
Contact: Pascal RISCHMANN, Pr    05 61 32 25 33 ext +33    rischmann.p@chu-toulouse.fr   
Sponsors and Collaborators
Hospices Civils de Lyon

Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03531099     History of Changes
Other Study ID Numbers: 69HCL18_0203
First Posted: May 21, 2018    Key Record Dates
Last Update Posted: September 19, 2018
Last Verified: September 2018

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

Keywords provided by Hospices Civils de Lyon:
Prostate cancer
HIFU focal
adverse effect
low risk

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases