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

NCT ID: NCT03531099

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 108 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-02
• Study Completion Date: 2026-10-02

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

treatment with focal HIFU

Intervention Type: PROCEDURE

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.

PSA dosage

Intervention Type: BIOLOGICAL

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

MRI

Intervention Type: DEVICE

MRI exam will be regularly performed during patient follow up.

Questionnaires

Intervention Type: OTHER

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)

Prostatic biopsies

Intervention Type: PROCEDURE

Prostatic biopsies will be regularly performed during patient follow up.

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.

Group Type: ACTIVE_COMPARATOR

PSA dosage

Intervention Type: BIOLOGICAL

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

MRI

Intervention Type: DEVICE

MRI exam will be regularly performed during patient follow up.

Questionnaires

Intervention Type: OTHER

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)

Prostatic biopsies

Intervention Type: PROCEDURE

Prostatic biopsies will be regularly performed during patient follow up.

Interventions

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.

Intervention Type: PROCEDURE

PSA dosage

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

Intervention Type: BIOLOGICAL

MRI

MRI exam will be regularly performed during patient follow up.

Intervention Type: DEVICE

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)

Intervention Type: OTHER

Prostatic biopsies

Prostatic biopsies will be regularly performed during patient follow up.

Intervention Type: PROCEDURE

Eligibility 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Polyclinique du parc Rambot

Aix-en-Provence, , France

Clinique Saint-Vincent

Besançon, , France

Service d'Urologie, Clinique Tivoli Ducos

Bordeaux, , France

Groupe Hospitalier Pellegrin - CHU

Bordeaux, , France

Service d'Urologie, CHU de Guebwiller Colmar

Colmar, , France

Service d'Urologie CHRU de Lille, Hôpital HURIEZ

Lille, , France

Service d'Urologie Générale de Santé - Hôpital Privé La Louvière

Lille, , France

Service d'Urologie et Chirurgie de la Transplantation, Hôpital Edouard Herriot,

Lyon, , France

Service d'urologie Assistance Publique - Hôpitaux de Marseille - Hôpital Marseille Nord

Marseille, , France

Département d'Urologie, Institut Montsouris

Paris, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

Clinique Urologique Nantes Atlantis

Saint-Herblain, , France

Service d'Urologie, Hôpital Foch

Suresnes, , France

CHU de Toulouse - Hôpital de Rangueil

Toulouse, , France

Countries

France

Other Identifiers

2018-A01024-51

Identifier Type: OTHER

Identifier Source: secondary_id

69HCL18_0203

Identifier Type: -

Identifier Source: org_study_id