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

NCT03531099 | Active Not Recruiting Phase 3 DMC

• 2 other identifiers: 69HCL18_02032018-A01024-51
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 14

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

Keywords

Prostate cancer; HIFU focal; adverse effect; low risk

Outcome Measures

Primary Outcomes (1)

• patient proportion who needed to seek radical treatment

  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.

  48 month

Secondary Outcomes (23)

• proportion of patients needing additional treatment

  24 months

• proportion of patients needing additional treatment

  48 months

• rate of positive biopsies

  24 months

• rate of positive biopsies

  48 months

• clinically significant cancer rate

  24 months

Study Arms (2)

HIFU treatment

EXPERIMENTAL

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; Biological: PSA dosage; Device: MRI; Other: Questionnaires; Procedure: Prostatic biopsies

Active surveillance

ACTIVE COMPARATOR

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; Device: MRI; Other: Questionnaires; Procedure: Prostatic biopsies

Interventions

treatment with focal HIFU 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.

HIFU treatment

PSA dosage BIOLOGICAL

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

Active surveillance; HIFU treatment

MRI DEVICE

MRI exam will be regularly performed during patient follow up.

Active surveillance; HIFU treatment

Questionnaires 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)

Active surveillance; HIFU treatment

Prostatic biopsies PROCEDURE

Prostatic biopsies will be regularly performed during patient follow up.

Active surveillance; HIFU treatment

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (14)

Polyclinique du parc Rambot

Aix-en-Provence, 13100, France

Location

Clinique Saint-Vincent

Besançon, 25044, France

Location

Service d'Urologie, Clinique Tivoli Ducos

Bordeaux, 33000, France

Location

Groupe Hospitalier Pellegrin - CHU

Bordeaux, 33076, France

Location

Service d'Urologie, CHU de Guebwiller Colmar

Colmar, 68024, France

Location

Service d'Urologie CHRU de Lille, Hôpital HURIEZ

Lille, 59000, France

Location

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

Lille, 59000, France

Location

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

Lyon, 69437, France

Location

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

Marseille, 13915, France

Location

Département d'Urologie, Institut Montsouris

Paris, 75014, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Clinique Urologique Nantes Atlantis

Saint-Herblain, 44800, France

Location

Service d'Urologie, Hôpital Foch

Suresnes, 92150, France

Location

CHU de Toulouse - Hôpital de Rangueil

Toulouse, 31400, France

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Therapeutics; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 21, 2018
• Study Start: October 2, 2018
• Primary Completion: October 2, 2025
• Study Completion (Estimated): October 2, 2026
• Last Updated: June 22, 2025

Record last verified: 2025-06

Locations

FR (14)