Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Androgens

After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.

Degarelix is injected subcutaneously into the fatty tissue of the abdomen. A typical protocol consists of a starting dose of 240 mg with a maintenance dose of 80 mg administered every 28 days. In this study, one starting dose and two maintenance doses of Degarelix will be administered between baseline and TULSA treatment in accordance with the terms of Degarelix marketing authorizations.

Degarelix

MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) will be used to deliver whole-prostate gland treatment in accordance with the terms of TULSA marketing authorizations. The treating physicians will contour the entire prostate gland for a whole gland ablation.

MRI-guided transurethral ultrasound ablation (TULSA)

Mikael HJ Anttinen, MD, PhD

Kaisa Reunanen

Clinical studies have shown that magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate is safe and effective. In the TULSA procedure, prostate tissue is killed by heating with ultrasound. This clinical trial explores if adding drug therapy with Degarelix before TULSA has the potential to improve further the effectiveness of TULSA in the treatment of localized prostate cancer, especially for patients with more aggressive diseases.

Androgen deprivation therapy (ADT) has been shown to reduce prostate and tumor size. In this study, magnetic resonance imaging (MRI) is used to investigate the effect of Degarelix ADT on the properties of prostate tissue that can affect the heating of the tissues in the TULSA procedure. The main goal is to find out if ADT can change the tissue structure in a way that improves the ability of the TULSA procedure to heat tissues and better kill the diseased tissue, reducing the chance of the disease reoccurring. ADT and the TULSA procedure can help patients with more aggressive diseases avoid the adverse effects associated with surgery or radiation therapy. Specific objectives are:

1. To measure the change in prostate and tumor size, tissue structural changes, and the blood flow within the prostate after ADT.
2. To measure the distribution of heating over the prostate after TULSA treatment.
3. To evaluate complications and genitourinary function and quality of life with patient-reported outcome measures.
4. To evaluate local cancer control and longer-term oncological outcomes after combination therapy of neoadjuvant ADT and TULSA treatment.

About 15 subjects will participate. Each will receive Degarelix for three months, followed by whole-prostate gland TULSA treatment, and be followed for five years. Throughout the study, subjects will receive MRI scans and complete questionnaires regarding functional status and quality of life to understand the side effects.

Procedure: Magnetic resonance imaging-guided transurethral ultrasound ablation of the prostate (TULSA)

Drug: Degarelix

Neoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer

Effect of Neoadjuvant Degarelix on MRI-guided Transurethral Ultrasound Ablation (TULSA) in Patients With Intermediate-risk Prostate Cancer: A Pilot Study

The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at three, and 12 months after TULSA to that at TULSA procedure.

The change in maximum urinary flow rate (Qmax) (ml/s) will be determined by comparing Qmax values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.

The change in average urinary flow rate (ml/s) will be determined by comparing average flow rate values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.

The change in post-void residual volume (PVR) (ml) will be determined by comparing PVR values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.

The change in voided volume (ml) will be determined by comparing voided volume values at 12 weeks of ADT and three, 12, 36, and 60 months post-TULSA to that at baseline and TULSA procedure.

3T prostate multiparametric MRI three and twelve months after TULSA treatment will be assessed for residual or recurrent disease according to the Prostate Imaging for Recurrence Reporting (PI-RR) system guidelines. The proportion of subjects with a suspicious lesion on MRI, defined as lesion ≥ PI-RR 3, will be reported.

The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

The prostate tumor volume change will be determined by comparing the prostate tumor volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined by using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.

The prostate tumor-capsule contact length change will be determined by comparing the prostate tumor-capsule contact length measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

The change in prostate vascular perfusion will be determined by comparing average blood flow values in the prostate measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

The change in prostate tumor vascular perfusion will be determined by comparing average blood flow values in the prostate tumor measured on dynamic contrast-enhanced T1-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.

The change in periprostatic, prostate and tumor tissue structures will be determined by comparing the radiomics features extracted from T2-weighted, T2 relaxation time mapping, and diffusion-weighted images at four, eight, and 12 weeks of ADT to that at baseline.

Thermal coverage of the target volume achieved by whole-prostate gland TULSA will be determined by comparing physician-defined target boundaries to MRI measurements of temperature distributions, thermal dose distributions, and acute treatment-induced perfusion defect immediately post-treatment.

The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite-26 (EPIC-26) questionnaire at 12 weeks of ADT to that at baseline. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.

The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at 12 weeks of ADT to that at baseline. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.

The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at 12 weeks of ADT to that at baseline. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.

The change in QoL and functional status outcomes will be determined by comparing the summary scores of urinary incontinence, urinary irritative/obstructive, bowel, sexual and hormonal domains of the Expanded Prostate Index Composite (EPIC-26) questionnaire at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. EPIC-26 contains 26 items with response options for each EPIC item forming a Likert Scale, and multi-item scale scores transformed linearly to a 0-100 scale, with higher scores representing better functional status/QoL.

The change in lower urinary tract symptoms will be determined by comparing the International Prostate Symptom Score (IPSS) at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IPSS questionnaire range from 0 to 35, with higher scores representing worse symptoms.

The change in erectile function will be determined by comparing the International Index of Erectile Function (IIEF-5) score at three, six, 12, 36 and 60 months post-TULSA to that at baseline and TULSA procedure. The possible scores for the IIEF-5 range from 5 to 25, with higher scores representing a better erectile function.

The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.

Salvage therapy-free survival will be defined as freedom from radical salvage treatments for prostate cancer including radical prostatectomy, radiotherapy, or ablation, and reported as the proportion of subjects who have not reached those events.

Systemic therapy-free survival will be defined as freedom from additional systemic therapy including but not limited to additional ADT or chemotherapy for the treatment of prostate cancer, and reported as the proportion of subjects who have not reached those events.

Failure-free survival will be defined as freedom from salvage treatment, systemic treatment, metastases, or death from prostate cancer, and reported as the proportion of subjects who have not reached those events.

Metastasis-free, prostate cancer-specific and overall survivals will be assessed one, three, and five years after TULSA and reported as the proportion of subjects who have not reached those endpoints.

PSA at each timepoint, as well as PSA nadir, will be reported. The proportion of subjects with biochemical failure, defined as a PSA value more than 2.0 ng/ml above nadir, will be reported.

Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The proportion of subjects with a clinically-significant disease, defined as Gleason grade ≥ 3 + 4 and ISUP (International Society of Urological Pathology) grade group ≥ 2 prostate cancer, on biopsy, will be reported.

Histopathologic verification of treatment response to TULSA treatment will be confirmed at 12 months post-TULSA with targeted plus 10-12-core systematic biopsy. The number, location, grade, and percent of cancer involvement within each core will be collected. The proportion of subjects with any prostate cancer on biopsy, will be reported.

Turku University Hospital

Nervous System Diseases

Rare Diseases

Glioma

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

Carboplatin

SonoCloud® : dose escalation 6 cycles of sonication

SonoCloud®, sonication: dose escalation 6 cycles of sonication

SonoCloud® (9 transducers)

Kevin BECCARIA, MD, PhD

Nelly BRIAND, MD, PhD

Franck BOURDEAUT, MD, PhD

Franck BOURDEAUT

Kevin BECCARIA

Jacques GRILL, MD, PhD

Jacques GRILL

Purpose : the aim of this study is to assess the feasibility and safety of ultrasound-induced opening of the blood-brain barrier (BBB) with the SonoCloud-9 implantable ultrasound device in pediatric patients treated for a recurrent malignant supra-tentorial brain tumor treated with carboplatin.

Study hypothesis : the blood-brain barrier can be transiently and safely opened with pulsed low intensity ultrasound immediately prior to intravenously delivered chemotherapy. The opening of the BBB with the SonoCloud-9 system will increase the tumor exposure to carboplatin and increase progression-free and overall survival in pediatric patients treated for a recurrent malignant supra-tentorial brain tumor.

Malignant brain tumors are the first cause of death by cancer in children and adolescents. The dismal prognosis of malignant brain tumors is partially due to the existence of the blood brain barrier (BBB), a physiological barrier that limits the penetration of almost all molecules from the blood stream to the brain, including antineoplastic drugs.

It has been shown that the application of low intensity ultrasound on the brain in association with intravenous microbubbles leads to transient and safe opening of the BBB. Many preclinical studies have demonstrated that ultrasound-induced opening of the BBB increases the distribution of therapeutic molecules into the brain and allows tumor control and increases survival in animal models (mice, rabbits, pigs, primates).

An innovative implantable ultrasound system, the SonoCloud device, has been developed in order to repeatedly open the BBB in synchronization with chemotherapy protocols.

This intracranial and subcutaneous device is not visible and MRI compatible and allows repeatable and ambulatory treatments. Moreover, such a device allows the delivery of low intensity ultrasound in a controlled and reproductible manner.

A phase I/IIa trial has confirmed the feasibility and safety of this technique in adult patients treated for recurrent glioblastoma with carboplatin-based chemotherapy.

This study will assess the feasibility and safety of ultrasound-induced opening of the BBB with the SonoCloud device in pediatric patients treated with carboplatin chemotherapy for a recurrent supra-tentorial malignant brain tumor. The study will determine the maximum tolerated ultrasound acoustic pressure that can be used for BBB opening and the safety of the activation of 3, then 9 transducers with the SonoCloud-9® device. Patients will follow 6 months cycles of treatment. If the treatment is well tolerated, patients will be able to be treated for 6 more cycles.

The magnitude and intensity of the BBB opening, its clinical (overall survival) and radiological (progression-free survival) efficacy will be assessed as secondary endpoints. Safety of the ultrasound contrast agent SonoVue will also be evaluated in this indication in the pediatric population.

An ancillary study will assess circulating tumor DNA (ctDNA) concentrations in patients with recurrence of a supra-tentorial malignant brain tumor, at diagnosis and during repeated opening of the BBB. The study will assess the correlation between ctDNA concentrations and tumor evolution.

Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients

Phase I Trial Assessing the Safety of the Repeated Ultrasound-induced Opening of the Blood-brain Barrier in Pediatric Patients With Refractory Supra-tentorial Malignant Brain Tumors Before Chemotherapy Administration

Clinical evaluation (neurological deficit, intracranial hypertension, epilepsy) during acoustic pressure dose escalation, after each sonication (48h)

Radiological evaluation (hemorrage, ischemia, brain swelling) during acoustic pressure dose escalation, after each sonication

Grading of BBB disruption using the scale previously described (Carpentier et al 2016), after each sonication

Progression Free Survival (PFS) using RANO Criteria

Allergic reactions (cutaneous eruption, oedema, respiratory failure) in relation to the use of the ultrasound contrast agent SonoVue® for BBB disruption in the pediatric population, during and after each sonication

Cardiac reactions (thoracic pain, cardiac failure, EKG modification) in relation with the use of the ultrasound contrast agent SonoVue® for BBB disruption in the pediatric population, during and after each sonication

Complications associated with the implantation of the SonoCloud® device : acute pain evaluation using VAS (Visual Analogue Scale) for patients \>_ 7 years old or using behavioral pain scale EVENDOL for patients \<7 years old, immediately after implantation

Complications associated with the implantation of the SonoCloud® device : acute pain evaluation using VAS (Visual Analogue Scale) for patients \>_ 7 years old or using behavioral pain scale EVENDOL for patients \<7 years old, at day 1 after implantation

Complications associated with the implantation of the SonoCloud® device : chronic pain evaluation using VAS (Visual Analogue Scale) for patients \>_7 years old or using behavioral pain scale EVENDOL for patients \<7 years old, monthly, before each new cycle of treatment

Complications associated with the implantation of the SonoCloud® device using radiological examination : device position and post-operative complication (hematoma), one day after implantation

Assessment of complications associated with the sonications : pain evaluation using VAS (Visual Analogue Scale) for patients \>_ 7 years old or using behavioral pain scale EVENDOL for patients \<7 years old at needle connexion

Complications associated with the implantation of the SonoCloud® device : pain evaluation using VAS (Visual Analogue Scale) for patients \>_ 7 years old or using behavioral pain scale EVENDOL for patients \<7 years old, during sonication

Assessment of skin complications associated with sonications : eschar and/or infection, before each cycle of treatment

Process evaluated by the surgeon: number of tests necessary for needle connexion to the device, at each sonication

Process evaluated by the surgeon : duration from needle connexion to the end of sonication, at each sonication

Process evaluated by the surgeon : duration for device implantation

Histological analysis of tissue around the device : thickness, inflammation, biocompatibility, at explantation

Physical analysis of the device, at explantation

Evaluation of the effect of BBB disruption with the SonoCloud-9® device on the circulation of tumoral components in the blood flow, at each cycle of treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Neoadjuvant ADT With TULSA in the Treatment of Intermediate Risk Prostate Cancer	NCT05917860	Localized Prost... Castration-Naiv... Intermediate Ri... Prostate Cancer	Degarelix MRI-guided tran...	40 Years - 80 Years	Turku University Hospital
Safety Study of the Repeated Opening of the Blood-brain Barrier With the SonoCloud® Device to Treat Malignant Brain Tumors in Pediatric Patients	NCT05293197	Malignant Brain... Malignant Gliom... Embryonal Tumor	SonoCloud® (9 t...	5 Years - 17 Years	Assistance Publique - Hôpitaux de Paris

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