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

• ClinicalTrials.gov Identifier: NCT03568188
• Recruitment Status: Recruiting
• First Posted: June 26, 2018
• Last Update Posted: March 16, 2022
• Sponsor: Hospices Civils de Lyon
• Information provided by (Responsible Party): Hospices Civils de Lyon

Study Description

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 170 participants
• Allocation: N/A
• 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, 2022
• Estimated Study Completion Date: September 28, 2025

Arms and Interventions

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.

Outcome Measures

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.

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 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.

Contacts and Locations

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

Polyclinique du parc Rambot; 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; 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

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

Additional Information:

Related Info 

• 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
• Last Update Posted: March 16, 2022
• Last Verified: March 2022

• 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:

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