Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioblastoma

Astrocytoma

Glioma

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

All Drugs and Chemicals

Carboplatin

Temozolomide

Lomustine

Antineoplastic Agents, Alkylating

Alkylating Agents

The SonoCloud-9 (SC9) device will be implanted in the skull bone window upon completion of tumor resection and routine craniotomy. Carboplatin (CBDCA) will be administered intravenously prior to sonication. The CBDCA/SC9 treatment will be repeated every 3 weeks (depending on patient's tolerability) until disease progression or as clinically indicated. Administration of up to 7 cycles is planned.

Standard of Care (SoC) treatment with either temozolomide (TMZ) or lomustine (CCNU).

Standard TMZ chemotherapy as a single oral dose every 4 weeks for up to 6 cycles.

Standard CCNU chemotherapy as a single oral dose every 6 weeks for up to 4 cycles.

Implantation of SC9 device and repeat activation at constant acoustic pressure

SonoCloud-9 (SC9)

Dose of carboplatin AUC 5 mg/ml.min-1 calculated using Calvert's formula:

Dose (mg) = target AUC (mg/mL x minute) x \[glomerular filtration rate (GFR) mL/minute + 25\].

Carole Desseaux

Rimas Lukas, MD

Kathryn Nevel

Brian JA Gill, MD

Dominique Higgins, MD

Duerinck Johnny, MD

Steven de Vleeschouwer, MD

Pierre Frères, MD

François Ducray, MD

Olivier Chinot, MD

Ahmed Idbaih, MD

Roland Goldbrunner, MD

Giuseppe Lombardi, MD

Martin van den Bent, MD

Angel Perez-Nunez, MD

The brain is protected from any toxic or inflammatory molecule by the blood-brain barrier (BBB). This physical barrier is located at the level of the blood vessel walls. Because of these barrier properties, the blood vessels are also impermeable to the passage of therapeutic molecules from the blood to the brain. The development of effective treatments against glioblastoma is thus limited due to the BBB that prevents most drugs injected in the bloodstream from getting into brain tissue where the tumour is seated. The SonoCloud-9 (SC9) is an investigational device using ultrasound technology and specially developed to open the BBB in the area of and surrounding the tumour. The transient opening of the BBB allows more drugs to reach the brain tumour tissue. Carboplatin is a chemotherapy that is approved to treat different cancer types alone or in combination with other drugs, and has been used in the treatment of glioblastoma. Despite its proven efficacy in the laboratory on glioblastoma cells, carboplatin does not readily cross the BBB in humans. A clinical trial has shown that in combination with the SonoCloud-9, more carboplatin can reach the brain tumour tissue. The objective of the proposed trial is to show that the association - carboplatin with the SonoCloud-9 - will increase efficacy of the drug in patients with recurrent glioblastoma.

Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM

A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma.

Frequency and severity of adverse events scored according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0, from surgery to End-of-Trial Intervention visit

Survival status will be collected during the treatment period, for up to 7 months (short-term follow-up) and then every 3 months as standard of care follow-up (long-term follow-up) until participant's 'End of Study', defined as end of survival follow-up period, death, withdrawal of consent for the collection of data, or 'lost to follow-up' (whichever comes first).

Tumor Growth Rate will be determined by measuring hyperintense tumor volume using T1w contrast-enhancing tumor-related region from post-surgery MRI baseline to unequivocal progression MRI (i.e., suspected radiologic progression confirmed by repeat scan).

Defined as the time from date of randomization to the earlier of the following events: unequivocal tumor progression as determined by IRC per RANO criteria or death due to any cause.

Defined as the proportion of participants alive at 12 months

Defined as the proportion of participants alive at 18 months

Defined as the proportion of participants without disease progression or death due to any cause at 6 months.

CarThera

Gliosarcoma

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Patients will undergo implantation of Sonocloud-9 after completion of radiotherapy. Within 21 days after implant, ultrasound-based BBB opening with concomitant administration of DOX (30 mg) + BAL (450 mg) every 3 weeks, and BOT (dose 1mg/kg) every 6 weeks will be initiated.

Balstilimab 450 mg IV over 30 minutes every 3 weeks

Balstilimab

Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

Botensilimab

Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

Liposomal Doxorubicin

Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks

Sonocloud-9 (SC-9)

Christina Amidei

Nicole Morud

Adam Sonabend, MD

Roger Stupp, MD

Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB.

The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.

Eligible patients will undergo implant of the Soncloud-9 device within 1-5 weeks of completion of radiotherapy. About 1-3 weeks after surgery, patients will undergo sonication and intravenous administration of balstilimab, botensilimab and liposomal doxorubicin. Brain MRI will be done to quantify extent of blood brain barrier opening. The dose for balstilimab is 450 mg every 3 weeks. The dose for botensilimab is 1mg/kg every 6 weeks. The dose for liposomal doxorubicin is 30 mg every 3 weeks. Sonication and administration of study agents will continue every 3 weeks (21 days= 1 cycle) for a total of 9 cycles (approx. 6 months). Additional cycles may be considered if deemed beneficial and in the patient's best interest. Blood samples for circulating tumor DNA will also be collected before and after each sonication. The first 6 patients will comprise a safety run-in cohort with intensified safety monitoring through the end of the second cycle.

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma

Patterns of recurrence by magnetic resonance imaging related to sonication field

Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival

Unacceptable toxicity rate in cycle 1 of \< 33%

Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival.

Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy

Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor

Agenus Inc.

Northwestern University

Principal Investigator

Disease Attributes

Paclitaxel

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Infusion of albumin-bound paclitaxel immediately followed by sonication using the SC9 device and microbubbles in order to open the blood-brain barrier in phase 1. In phase 2, patients will receive carboplatin immediately prior to sonication using the SC9 device and microbubbles in order to open the blood-brain barrier, then will receive albumin-bound paclitaxel upon completion of sonication.

Implantation of SC-9 device and repeat activation of 9 ultrasound emitters during i.v. injection of microbubbles

Sonication for opening of blood-brain barrier

Intravenous infusion of ABX over 30 minutes

Chemotherapy, albumin-bound paclitaxel

Intravenous infusion of carboplatin over 30 minutes

Chemotherapy, carboplatin

Christina Amidei, APN, PhD

Christina Amidei, PhD, APN

Adam M Sonabend, MD

Karan Dixit, MD

Priya Kumthekar, MD

Rimas V Lukas, MD

Paclitaxel is among the most active agents against glioblastoma in preclinical models. However, its clinical use has been hampered by the blood-brain barrier (BBB). In this trial we will implant a novel device with 9 ultrasound emitters allowing to temporarily and reversibly open the BBB immediately prior to chemotherapy infusion with albumin-bound paclitaxel.

In the phase 1 component, increasing doses of chemotherapy will be delivered as long deemed safe based on the prior patient not experiencing severe toxicity. Once the the recommended dosing has been established, carboplatin will be added to the regimen and additional patients will be treated in order to better evaluate the antitumor efficacy of this novel treatment.

The device will be implanted at the time of surgical resection of the recurrent tumor. During that procedure and when feasible, a first test dose of the chemotherapy will be administered in the operating room after sonication (procedure of activating ultrasound and opening the BBB) and tissue concentrations in different parts of the resected tumor will be measured. In select patients, the sonication procedure may occur immediately after the test dose of chemotherapy is administered.

The objectives of this trial are to establish a safe and effective dose of albumin-bound paclitaxel, to demonstrate that the opening of the BBB increases chemotherapy concentration in the tumor, and to estimate how effective this treatment is in reducing the tumor burden and prolonging life.

Eligible patients will undergo craniotomy for tumor resection. During the tumor resection and when possible, an initial low dose of albumin-bound paclitaxel will be given following sonication. In select patients, the sonication procedure may occur immediately after the test dose of chemotherapy is administered. The sonication device will be implanted at the end of the procedure. In phase 1, about two weeks after surgery, patients will undergo sonication and albumin-bound paclitaxel administration with MRI to quantify extent of blood brain barrier opening. Sonication and administration of albumin-bound paclitaxel will continue every 3 weeks until disease progression. The planned albumin-bound paclitaxel starting dose is 40 mg/m2, to be escalated in the absence of significant toxicity up to 260 mg/m2. Blood samples for circulating tumor DNA will also be collected before and after each sonication. In phase 2, pre-sonication carboplatin at AUC 5 will be added to the regimen, with a safety run-in for the first 6 patients.

Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin for Recurrent Glioblastoma

Phase 1 / 2 Trial of Blood-brain Barrier Opening With an Implantable Ultrasound Device SonoCloud-9 and Treatment With Albumin-bound Paclitaxel and Carboplatin in Patients With Recurrent Glioblastoma

increase in Gd contrast enhancement post sonication

measurement of tumor shrinkage (if there is residual disease)

Occurrence of ≥ grade 3 treatment related toxicity

Survival time from date of tumor resection and device implantation

Bristol-Myers Squibb

Lantheus Medical Imaging

Assistant Professor, Feinberg School of Medicine, Neurological Surgery

Skin and Connective Tissue Diseases

Nervous System Diseases

Neoplasm Metastasis

Melanoma

Brain Neoplasms

Neuroendocrine Tumors

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

SonoCloud® is an active implantable device (implantation duration until 16 weeks at maximum after inclusion). SonoCloud® delivers low intensity pulsed UltraSound (US). Along with systemic injection of an US resonator, SonoCloud® demonstrated safe and efficient at repetitively opening the BBB.

The SonoCloud System is an active implantable medical. The SonoCloud is indicated to locally and transiently increase the permeability of the blood brain barrier to facilitate the passage of substances into the cerebral parenchyma.

The SonoCloud System consists of :

1. an implantable ultrasound transducer,
2. a needle connection device,
3. an external radiofrequency generator, and
4. an ultrasound resonator. The SonoCloud® is designed to be fixed to the skull. The device is placed in a burr hole or in place of a bone flap and ultrasound energy is delivered directly to the brain tissue, without traversing the skull bone. The device is activated by connecting the implant to the external generator system using the transdermal needle. Once connected to the external generator, the implant delivers low-intensity pulsed UltraSound (US) for duration of 120-270 seconds. A total of 3 US dose levels will be evaluated (0.78, 0.9 and 1.03 MPa).

SONOCLOUD

Nivolumab (flat dose: 240mg, 30 minutes infusion)

Nivolumab Injection

LEBBE Celeste, MD, PhD

Matthieu RESCHE-RIGON, MD PhD

Celeste LEBBE, MD-PHD

El-Mountacer el-abbassi

Anti PD-1 monoclonal antibodies (nivolumab and pembrolizumab) alone or in association with antiCTLA4 (Ipilimumab) are established as indisputable treatment of metastatic melanoma, with unprecedented overall survival, and are indicated for first-line treatment including patients with BRAF mutation. Given their high molecular weight, their penetration in the brain sanctuary is uncertain and relies on disruption of the Blood Brain Barrier (BBB) which occurs occasionally.

SonoCloud® is an implantable device delivering low intensity pulsed UltraSound (US). Along with systemic injection of an US resonator, SonoCloud® demonstrated safe and efficient at repetitively opening the BBB. The investigators anticipate that BBB opening could help at increasing brain penetration of monoclonal antibodies and potentially boosting immunity in the brain. This could translate in controlling brain disease with the same magnitude as for extra-cranial disease. This would also open avenues for optimizing the treatment of brain metastases in combination with checkpoint inhibitors in many other cancers.

Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma

Safety and Efficacy of Blood Brain Barrier Opening With Implantable Device Sonocloud® Combined With Nivolumab Used Alone or an Association With Ipilimumab in Brain Metastases From Patients With Malignant Melanoma

Dose with the highest probability of BBB opening efficacy without toxicity directly related to the ultrasound emission.

Toxicity evaluation:

Safety will be assessed clinically and using brain Magnetic resonance imaging (MRI). An electroencephalogram will be performed only if clinically needed. Dose-Limiting-Toxicities (DLTs) evaluation will be done during the first 4 weeks of treatment for Nivolumab treatment and 6 weeks for Nivolumab + Ipilimumab treatment. DLTs directly related to the ultrasound emission are defined as occurrence of an adverse effect during the first administration of treatment, such as: :

* neurological deficit within 2 days after the procedure and persistent at day 15;
* localized brain edema not preexisting to the procedure;
* occurrence of cerebral median line deviation not controlled by routine treatment or requiring salvage surgical procedure;
* partial epilepsy induced or enhanced after the procedure and not control

Best clinical objective response (BOR) (defined with the Response assessment in neuro-oncology criteria (RANO) and immunotherapy response assessment for neuro-oncology (iRANO) and the response evaluation criteria in solid tumours (RECIST) version 1.1 and the Immune-Related Response Criteria during the 3 first months

RANO : Wen, Patrick Y., et al. "Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group." J Clin Oncol 28.11 (2010): 1963-1972.

iRANO : Okada, Hideho, et al. "Immunotherapy response assessment in neuro-oncology: a report of the RANO working group." The Lancet Oncology 16.15 (2015): e534-e542.

Clinical objective response (defined with the RANO and iRANO and the RECIST version 1.1 and the Immune-Related Response Criteria) during the 3 first months

Clinical efficacy will be assessed using TEP/TDM Scans (extracranial lesions) and MRI (intracranial metastases) at Month 3

Best clinical objective response rate not taking account BICORR

Clinical objective response not taking account ICORR

Assistance Publique - Hôpitaux de Paris

SonoCloud-9 Carboplatin: 6 cycles (every 4 weeks)

Escalating numbers of ultrasound beams at constant acoustic pressure

SonoCloud-9

Ahmed IDBAIH, MD

Recurrent glioblastoma (GBM) is a disease with high unmet clinical need. The standard of care for patients with GBM includes surgery, radiotherapy and chemotherapy. Despite this aggressive treatment, the overall median survival of patients with GBM remains at 15-20 months.

In more than 95% of cases, tumor recurrence is observed within 2 cm to 3 cm of the resection cavity within 4-7 months after initial treatments. One of the main causes of recurrence is the inability of chemotherapies to enter the brain from the systemic circulation due to the blood-brain barrier (BBB). The BBB is unique to cerebral blood vessels and blocks most drugs from entering the brain in sufficient concentrations.

The SonoCloud-9 (SC9) System delivers ultrasound to locally and transiently increase the permeability of the BBB to allow the passage of drugs into the cerebral parenchyma. The SC9 is dimensioned to cover the resection area and surrounding tissues in patients with recurrent GBM. The large sonicated volume covered by the SC9 device allows for broad BBB disruption and should allow for carboplatin chemotherapy to penetrate the surrounding tumor infiltrative area. By enhancing drug concentrations, it is hypothesized that further disease progression will be prevented.

This will be an open-label, Phase 1/2a, multicenter, single-arm, interventional trial that will first evaluate the dose limiting toxicity (DLT) of escalating numbers of ultrasound beams at constant acoustic pressure using a standard escalation (Phase 1) and then confirm the safety and efficacy of BBB opening (Phase 2a expansion).

Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9

A Study to Evaluate the Safety and the Efficacy of Transient Opening of the Blood-brain Barrier (BBB) by Low Intensity Pulsed Ultrasound With the SonoCloud-9 Implantable Device in Recurrent Glioblastoma Patients Eligible for Surgery and for Carboplatin Chemotherapy

DLT will be evaluated using imaging (MRI) and clinical examination, as CTCAE that occurs within 2 weeks of the first sonication and that does not respond to optimal medical management (including steroids) within 7 days.

BBB opening will be evaluated by contrast-enhanced T1w magnetic resonance imaging (MRI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM	NCT05902169	Glioblastoma Recurrent Gliob... GBM	SonoCloud-9 (SC... Carboplatin Lomustine Temozolomide	18 Years -	CarThera
Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma	NCT05864534	Newly Diagnosed... Glioblastoma, I... Gliosarcoma Glioblastoma Mu...	Balstilimab Botensilimab Liposomal Doxor... Sonocloud-9 (SC...	18 Years -	Northwestern University
Sonocloud-9 in Association With Carboplatin Versus Standard-of-Care Chemotherapies (CCNU or TMZ) in Recurrent GBM	NCT05902169	Glioblastoma Recurrent Gliob... GBM	SonoCloud-9 (SC... Carboplatin Lomustine Temozolomide	18 Years -	CarThera
Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin for Recurrent Glioblastoma	NCT04528680	Glioblastoma Gliosarcoma GBM Glioblastoma Mu... Glioblastoma, I... Recurrent Gliob...	Sonication for ... Chemotherapy, a... Chemotherapy, c...	18 Years -	Northwestern University
Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin for Recurrent Glioblastoma	NCT04528680	Glioblastoma Gliosarcoma GBM Glioblastoma Mu... Glioblastoma, I... Recurrent Gliob...	Sonication for ... Chemotherapy, a... Chemotherapy, c...	18 Years -	Northwestern University
Safety and Efficacy of Sonocloud Device Combined With Nivolumab in Brain Metastases From Patients With Melanoma	NCT04021420	Melanoma Metastatic Mela...	SONOCLOUD Nivolumab Injec...	18 Years -	Assistance Publique - Hôpitaux de Paris
Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9	NCT03744026	Glioblastoma, A...	SonoCloud-9 Carboplatin	18 Years -	CarThera

Spots Global Cancer Trial Database for sonocloud

Every month we try and update this database with for sonocloud cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sonocloud

Every month we try and update this database with for sonocloud cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sonocloud cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.