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)

• ClinicalTrials.gov Identifier: NCT03531099
• Recruitment Status: Recruiting
• First Posted: May 21, 2018
• Last Update Posted: November 22, 2021
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

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 Design

• 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
• Actual Study Start Date: October 2, 2018
• Estimated Primary Completion Date: October 2, 2026
• Estimated Study Completion Date: October 2, 2026

Arms and Interventions

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.

Outcome Measures

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

Eligibility Criteria

• 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 G8 score > 14.

• Initial diagnosis of localized prostate cancer (T1c or T2a) with the following characteristics:

  • Only one Target tumor on MRI on a maximum of 2 contigous sextants. Case allowed:

    • If more than one target tumor on MRI, only one of them must be confirmed by targeted prostate biopsies.
    • If no target tumor on MRI, only 2 contigous sextants must be positive on prostate biopsies
  • A maximum tumor length> 3 mm or at least 3 positive biopsies on all biopsies performed (randomized biopsies and/or MRI/Ultrasound Fusion-Guided Prostate Biopsy).
  • Gleason 6 score (risk group 1 of the D'Amico classification).
  • Tumor positioned so that a safety distance of at least 9 mm from external sphincter can be defined during HIFU-FOCAL treatment in prostate tissue around the target.
• 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 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 if randomized in HIFU-F arm).
• 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.

Contacts and Locations

Contacts

Contact: Sébastien CROUZET, Pr; 04 72 11 03 25 ext +33; sebastien.crouzet@chu-lyon.fr

Contact: Estelle RICCI, study manager; 04 72 11 74 94 ext +33; estelle.ricci@chu-lyon.fr

Locations

France

Polyclinique du parc Rambot; Recruiting

Aix-en-Provence, France, 13100

Contact: David BARRIOL, MD, PhD 04 42 96 53 40 ext +33 david.barriol@gmail.com

Principal Investigator: David BARRIOL, MD, PhD

Clinique Saint-Vincent; 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; 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

Service d'Urologie, CHU de Guebwiller 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, Pr 03 20 44 42 35 ext +33 arnauld.villers@wanadoo.fr

Principal Investigator: Arnaud VILLIERS, Pr

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

Principal Investigator: Sébastien CROUZET, Pr.

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: Eric BARRET, MD, PhD 01 56 61 66 18 ext +33 Eric.Barret@imm.fr

Principal Investigator: Eric BARRET, MD, PhD

Centre Hospitalier Lyon Sud; Recruiting

Pierre-bénite, France, 69495

Contact: Alain RUFFION, Pr 04 72 67 88 08 ext +33 alain.ruffion@chu-lyon.fr

Principal Investigator: Alain RUFFION, Pr

Clinique Urologique Nantes Atlantis; 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, Pr 05 61 32 25 33 ext +33 rischmann.p@chu-toulouse.fr

Principal Investigator: Pascal RISCHMANN, Pr

Sweden

Clinique Générale Beaulieu - Swiss International Prostate Center; Not yet recruiting

Geneva, Sweden, 1206

Contact: REGUSCI Stefano, MD, PhD 22 343 92 12 ext +41 regusci@bluewin.ch

Principal Investigator: REGUSCI Stefano, MD, PhD

Sponsors and Collaborators

Hospices Civils de Lyon

More Information

• Responsible Party: Hospices Civils de Lyon
• ClinicalTrials.gov Identifier: NCT03531099
• Other Study ID Numbers: 69HCL18_0203; 2018-A01024-51 ( Other Identifier: ID-RCB )
• First Posted: May 21, 2018
• Last Update Posted: November 22, 2021
• Last Verified: November 2021

• 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; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases