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Efficacy Evaluation of Focused HIFU (High Intensity Focused Ultrasound) Therapy in Patients With Localized Intermediate Risk Prostate Cancer (FOCALE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03568188
Recruitment Status : Recruiting
First Posted : June 26, 2018
Last Update Posted : October 14, 2019
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Brief Summary:
The aim of the focal treatment HIFU is to destroy the cancer without causing side effects in contrast to radical treatments. Radical treatments (surgery or radiation therapy) are the standard therapies for patient with intermediate risk localized prostate cancer and good life expectancy (prostatectomy if life expectancy10 years) By destroying only the part of the gland that harbors cancer, it may indeed be possible to provide efficient cure of the disease while minimizing treatment-induced morbidity (incontinence and loss of potency). Around 20% of patients presented with a unilateral tumor: this patients are currently treated radically. No study published papers reported outcomes of a large population (>100) with intermediate risk cancers treated with Focal-HIFU (conducted with the Focal One® device). Focal therapy must be only offer within clinical trial setting (EAU (European Association of Urology) Guidelines ). The aim of this cohort will be to determine the success rate of Focal-HIFU in this intermediate risk population. The result the study will be used for calculation the arms of a future random study

Condition or disease Intervention/treatment Phase
Prostate Cancer Procedure: treatment with focal HIFU Biological: PSA dosage Device: MRI Other: Questionnaires Procedure: Prostatic biopsies Biological: blood test Biological: urine test Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2, Multicenter, Prospective Cohort Study, Estimating the Efficacy of Focused HIFU Therapy in Patients With Localized Intermediate Risk Prostate Cancer
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : September 28, 2021
Estimated Study Completion Date : September 28, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: HIFU treatment
170 patients with prostate cancer of intermediate risk receive the immediate treatment with focal HIFU. 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 will also have PSA (Prostate-Specific Antigen) dosage, MRI (Magnetic Resonance Imaging) exam, questionnaires and prostatic biopsies during their follow up. If the patient decides to participate in the ancillary study, a blood test (for immunological analyzes and detection of CTC (circulating tumor cells)) and a urine test (for PCA3 (The prostate cancer antigen 3 gene) test) will be performed 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).

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

Biological: blood test
if the patient decides to participate in the ancillary study, a blood test (for immunological analyzes and detection of CTC (circulating tumor cells)) will be performed during their follow up.

Biological: urine test
if the patient decides to participate in the ancillary study, a urine test (for PCA3 test) will be performed during their follow up.




Primary Outcome Measures :
  1. patient proportion with controlled disease (Control of the pathology) [ Time Frame: 12 months ]
    The main objective is the estimation of FOCAL HIFU treatment efficacy defined as the percentage of positive biopsies in the treated lobe at 12 months after inclusion.


Secondary Outcome Measures :
  1. proportion of patients needing additional treatment [ Time Frame: 12 months ]
    The objective is to determine the proportion of patients needing additional treatment (focal or radical) at 12 months. This includes patients who wish or require radical treatment (prostatectomy, radiotherapy), total focal treatment, or additional focal treatment.

  2. proportion of patients needing additional treatment [ Time Frame: 48 months ]
    The objective is to determine 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, or additional focal treatment.

  3. proportion of patients needing additional radical treatment [ Time Frame: 12 months ]
    The objective is to determine the proportion of patients needing additional radical treatment at 12 months. This includes patients who wish or require prostatectomy or radiotherapy total focal treatment.

  4. proportion of patients needing additional radical treatment [ Time Frame: 48 months ]
    The objective is to determine the proportion of patients needing additional radical treatment at 48 months. This includes patients who wish or require prostatectomy or radiotherapy total focal treatment.

  5. rate of positive biopsies [ Time Frame: 12 months ]
    The rate of positive biopsies in the untreated lobe and treated lobe evaluated and will be used to evaluate the carcinologic evolution at 12 months.

  6. 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 carcinologic evolution at 24 months.

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

  8. 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 carcinologic evolution at 48 months.

  9. Gleason score [ Time Frame: 12 months ]

    Evolution of the Gleason score (appearance of Gleason ≥7) will be measured and will be used to evaluate the carcinologic evolution at 12 month.

    The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.


  10. 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 carcinologic evolution at 24 month.

    The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.


  11. 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 carcinologic evolution at 48 month.

    The Gleason score is a prognosis factor for prostate cancer. It is based prostate cancer cells architecture from biopsies. The more the architectures of prostate cancer cell is destroyed, the worse is the prognosis. The score grades from 3 to 5, 5 being the more destroyed, the score 1 and 2 being normal cells. When there is more than one tumor cells population in the prostate, the score is composed of the sum of the most 2 frequents grade. For example a Gleason 7 tumor could be 3+4 or 4+3, the 4+3 being more aggressive.


  12. Appearance of another cancerous focus in the other half of the prostate [ Time Frame: 12 months ]
    Appearance of another cancerous focus in the other half of the prostate will be supervised and will be used to evaluate the carcinologic evolution at 12 months.

  13. 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 carcinologic evolution at 24 months.

  14. 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 carcinologic evolution at 48 months.

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

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

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

  18. Appearance of an extra capsular extension [ Time Frame: 12 months ]
    Appearance of an extra capsular extension will be supervised and will be used to evaluate the carcinologic evolution at 12 months.

  19. 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 carcinologic evolution at 24 months.

  20. 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 carcinologic evolution at 48 months.

  21. 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.

  22. 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

  23. 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.

  24. Proportion of serious adverse effect [ Time Frame: 48 months ]
    comparison of the proposition of serious adverse effect at 48 months

  25. Quality of life score [ Time Frame: over the 48 months ]

    quality of life will be assessed using the QLQC30 (Quality of Life questionnaire) questionnaire.

    It is a specific questionnaire to determine the quality of life a patient with cancer. It is composed of 30 questions with 4 potential answers going from: not at all, a little, enough or a lot, within 28 questions and with a visual scale going from 1 to 7 (7 being excellent and 1 being very bad) for the last 2 questions. The raw score is established by adding the score of each question and a linear transformation range it from 0 to 100. The higher the score, the better the quality of life.


  26. EPIC-26 score [ Time Frame: over the 48 months ]

    urinary function will be assessed using the EPIC-26 (The Expanded Prostate Cancer Index Composite) questionnaire.

    The EPIC-26 is a self-reported scale health-related quality of life questionnaire for prostate cancer patients . It is composed of 26 items in 4 different domains: urinary incontinence, urinary irritation/obstruction, bowel, sexual, and vitality/hormonal.

    Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale. Each items as a standardized value from 0 to 100. Then the average of the standardized value is determined in each domain to crate the summary score. The higher the score, the better the quality of life.


  27. IPSS score [ Time Frame: over the 48 months ]

    urinary function will be assessed using the IPSS (International Prostate Score Symptom) questionnaire.

    The IPSS questionnaire is based on the answers to seven questions concerning urinary symptoms and one question concerning quality of life. Each question concerning urinary symptoms allows the patient to choose one out of six answers indicating increasing severity of the particular symptom. The answers are assigned points from 0 to 5. The total score can therefore range from 0 to 35. The score is then categorized as follow: Mild (symptoms score less than or equal to 7), Moderate (symptom score range 8-19), Severe (symptom score range 20-35). The higher the score, the worse the symptoms.


  28. IIEF-5 score [ Time Frame: over the 48 months ]

    Sexual function will be assessed using the IIEF-5 (The International Index of Erectile Function) questionnaire.

    The IIEF-5 Questionnaire is composed of 5 items with 5 possible answers rating from 1 to 5 (very low, low, moderate, high, very high).

    The score is the sum of the ordinal responses to the 56 items. It is then categorized as follow: 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. The higher the score, the better the sexual function.


  29. patient proportion with controlled disease (Control of the pathology) [ Time Frame: 48 months ]
    The main objective is the estimation of FOCAL HIFU treatment efficacy defined as the percentage of positive biopsies in the treated lobe at 48 months after inclusion.

  30. Ancillary study: Measure of anti-tumoral immunity induction [ Time Frame: over the 48 months ]
    The consequences of HIFU treatment over immune anti-tumoral induction will be estimated by the description of Programmed death-ligand 1/ligand 2 (PDL1/L2) overexpression on immune cells and overexpression of Programmed cell death 1 (PD-1) on T lymphocytes (T-cells).

  31. Ancillary study: Measure of Circulating Tumor Cells (CTC) number reduction [ Time Frame: over the 48 months ]
    The consequences of HIFU treatment over Messenger RNA (mRNA) will be estimated by measure of CTC number reduction.

  32. Ancillary study: Measure of ncRNA (non-coding RNA) PCA3 (Prostate cancer gene 3) level reduction. [ Time Frame: over the 48 months ]
    The consequences of HIFU treatment over PCA3 will be estimated by measure of ncRNA PCA3 level reduction.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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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 G8 score > 14.
  • Initial diagnosis of localized prostate cancer (T1c 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.
    • Gleason score= 7 (3+4).
    • Tumor accessible to a Focal-HIFU treatment. For apical tumor, it must be localized more than 9 mm from the external sphincter
  • PSA ≤ 15ng / ml.
  • Patient affiliated with health insurance or beneficiary of an equivalent plan.

Exclusion Criteria:

  • Contraindications to treatment with HIFU-F:

    • Tumor not accessible.
    • 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.
  • TURP indication. Bladder neck incision is allowed.
  • 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 pelvic radiotherapy.
  • History of sclerosis of the bladder neck or urethral stenosis.
  • Patient with a several bleeding risk according to medical advice (patient with oral anticoagulant therapy must receive an alternative therapy).
  • 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): NCT03568188


Contacts
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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
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France
Polyclinique du parc Rambot Not yet recruiting
Aix-en-Provence, France, 13100
Contact: Eric ANFOSSI, MD, PhD    04 42 96 53 40 ext +33    eric.anfossi@wanadoo.fr   
Contact: David BARRIOL, MD, PhD    04 42 96 53 40 ext +33    david.barriol@gmail.com   
Sub-Investigator: David BARRIOL, MD, PhD         
Principal Investigator: Eric ANFOSSI, MD, PhD         
Clinique Saint-Vincent Not yet recruiting
Besançon, France, 25044
Contact: Vincent BAILLY, MD, PhD    03 10 00 14 80 ext +33    dr.bailly@mon-urologue.fr   
Principal Investigator: Vincent BAILLY, MD, PhD         
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   
Principal Investigator: Gilles PASTICIER, MD, PhD         
Groupe Hospitalier Pellegrin - CHU Not yet recruiting
Bordeaux, France, 33076
Contact: Franck BLADOU, PU, PH    05 57 82 03 40 ext +33    franck.bladou@chu-bordeaux.fr   
Principal Investigator: Franck BLADOU, PU, PH         
Hôpital L. Pasteur, Hôpitaux Civils de Colmar Recruiting
Colmar, France, 68024
Contact: Ludovic OBRINGER, MD, PhD    03 89 12 45 20 ext +33    obringerl@yahoo.fr   
Principal Investigator: Ludovic OBRINGER, MD, PhD         
Service d'Urologie CHRU de Lille, Hôpital HURIEZ Recruiting
Lille, France, 59000
Contact: Arnaud VILLIERS, PH    03 20 44 42 35 ext +33    arnauld.villers@wanadoo.fr   
Principal Investigator: Arnaud VILLIERS, PH         
Service d'Urologie Générale de Santé - Hôpital Privé La Louvière Recruiting
Lille, France, 59000
Contact: Pierre COLIN, MD, PhD    08 26 30 70 00 ext +33    docpierrecolin@gmail.com   
Principal Investigator: Pierre COLIN, MD, PhD         
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 Recruiting
Marseille, France, 13915
Contact: Harry TOLEDANO, MD, PHD    06 62 69 87 38 ext +33    harry.toledano@ap-hm.fr   
Principal Investigator: Harry TOLEDANO, MD, PHD         
Département d'Urologie, Institut Montsouris Recruiting
Paris, France, 75014
Contact: Rafael SANCHEZ SALAS, MD, PhD    01 56 61 66 18 ext +33    rafael.sanchez-salas@imm.fr   
Principal Investigator: Rafael SANCHEZ SALAS, MD, PhD         
Centre Hospitalier Lyon Sud - Hospices Civils de Lyon Recruiting
Pierre-Bénite, France, 69495
Contact: Alain RUFFION, Pu,PH    04 72 67 88 08 ext +33    alain.ruffion@chu-lyon.fr   
Principal Investigator: Alain RUFFION, Pu,PH         
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   
Principal Investigator: Eric POTIRON, MD, PhD         
Service d'Urologie, Hôpital Foch Recruiting
Suresnes, France, 92150
Contact: Tarek GHONEIM, MD, PhD    01 46 25 25 25 ext +33    t.ghoneim@hopital-foch.org   
Principal Investigator: Tarek GHONEIM, MD, PhD         
CHU de Toulouse - Hôpital de Rangueil Recruiting
Toulouse, France, 31400
Contact: Pascal RISCHMANN, PH    05 61 32 25 33 ext +33    rischmann.p@chu-toulouse.fr   
Principal Investigator: Pascal RISCHMANN, PH         
Sponsors and Collaborators
Hospices Civils de Lyon

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Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT03568188    
Other Study ID Numbers: 69HCL18_0292
2018-A01171-54 ( Other Identifier: ID-RCB )
First Posted: June 26, 2018    Key Record Dates
Last Update Posted: October 14, 2019
Last Verified: October 2019

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