Ultrasound-Assisted Chemotherapy for Glioblastoma

(SONOBIRD Trial)

Not currently recruiting at 50 trial locations

Overseen By Carole Desseaux

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: CarThera

Must not be taking: Corticosteroids, Anticoagulants, Antiepileptics, others

Disqualifiers: Multifocal tumor, Posterior fossa tumor, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating recurrent glioblastoma, a type of brain cancer. It combines a device called SonoCloud-9 (SC9) with chemotherapy drugs like carboplatin. SC9 uses ultrasound to temporarily open a barrier, allowing these drugs to reach the brain. The trial will compare this method with standard chemotherapy treatments to determine its effectiveness. Ideal candidates for this trial are those whose glioblastoma has returned after initial treatment and who are prepared for additional surgery to remove part of the tumor. As a Phase 3 trial, this study is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that patients on certain enzyme-inducing antiepileptic drugs must switch to another regimen. Additionally, those on anti-platelet or anticoagulation therapy may need to temporarily interrupt their medication after discussion with the sponsor.

What prior data suggests that the SonoCloud-9 device is safe for use in combination with carboplatin?

Research has shown that using the SonoCloud-9 device with the chemotherapy drug carboplatin is generally safe. One study found that the SonoCloud-9 can temporarily open the blood-brain barrier, allowing more carboplatin to reach brain tumors. Participants tolerated this process well. Another study demonstrated that this method effectively opened the barrier around a large tumor area without causing major side effects.

Carboplatin is already an approved treatment for other types of cancer, indicating its general safety. When combined with the SonoCloud-9, no significant additional risks were reported. These findings suggest that the treatment is well-tolerated, but discussing participation in a trial with a doctor is essential. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the ultrasound-assisted chemotherapy for glioblastoma because it offers a novel approach to treatment. Unlike standard care options like temozolomide (TMZ) or lomustine (CCNU), which are administered orally, this treatment combines the chemotherapy drug carboplatin with the SonoCloud-9 ultrasound device. This device is implanted in the skull and helps enhance the delivery of the drug directly to the brain, potentially increasing its effectiveness. This innovative method could improve drug penetration into the tumor, making it a game-changer in treating this aggressive form of brain cancer.

What evidence suggests that the SonoCloud-9 device is effective for opening the blood-brain barrier in glioblastoma treatment?

In this trial, participants in the experimental arm will receive the SonoCloud-9 ultrasound device combined with the drug carboplatin. Research has shown that this combination helps more of the drug reach brain tumor tissue. Glioblastoma, a type of brain cancer, is difficult to treat because the blood-brain barrier (BBB) usually prevents drugs from entering the brain. The SonoCloud-9 device uses ultrasound to temporarily open the BBB, allowing more carboplatin to reach the tumor. Previous studies suggest that increased carboplatin in the brain may enhance treatment effectiveness. This combination offers a promising approach for treating recurrent glioblastoma by potentially boosting the effects of chemotherapy. Meanwhile, the control arm will receive standard care with either temozolomide (TMZ) or lomustine (CCNU). ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with confirmed glioblastoma who've had prior surgery, radiotherapy, and chemotherapy can join. They must have a tumor that's grown after treatment but is less than 5 cm wide. Participants need good organ function, no severe allergies to trial drugs or device components, and not be on certain medications like anti-platelet drugs.

Inclusion Criteria

Adequate hematologic, hepatic, and renal laboratory values within 14 days of inclusion

I agree to use condoms and not donate sperm during treatment.

Patient of childbearing potential must have a negative pregnancy test within 14 days of inclusion and must agree to use a medically-acceptable method of birth control

Exclusion Criteria

I am at risk of getting an infection at my surgery site.

I do not have uncontrolled seizures or signs of high pressure inside my skull.

I do not have any serious health or mental conditions that could affect my treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either SonoCloud-9 with Carboplatin or standard chemotherapy (TMZ or CCNU). SonoCloud-9 with Carboplatin is administered every 3 weeks for up to 7 cycles, while TMZ is given every 4 weeks for up to 6 cycles, and CCNU every 6 weeks for up to 4 cycles.

Up to 24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival status collected during the treatment period and every 3 months thereafter.

Up to 24 months

Long-term follow-up

Participants continue to be monitored for overall survival and progression-free survival every 3 months as part of standard care follow-up.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• SonoCloud-9 (SC9)

Trial Overview The trial tests if using SonoCloud-9 (SC9), an ultrasound device designed to temporarily open the blood-brain barrier (BBB), increases the effectiveness of Carboplatin in treating recurrent glioblastoma compared to standard chemotherapies Lomustine or Temozolomide alone.

How Is the Trial Designed?

Group I: Experimental Arm: SonoCloud-9 Ultrasound + Carboplatin Experimental Treatment 2 Interventions

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.

Group II: Control Arm: SoC single agent chemotherapy TMZ or CCNU Active Control 2 Interventions

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.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

CarThera

Lead Sponsor

Trials

6

Recruited

710+

Published Research Related to This Trial

The interim results from a phase 1/2a clinical trial involving patients with recurrent glioblastoma show that using pulsed ultrasound to disrupt the blood-brain barrier (BBB) is safe and well tolerated, with no detectable adverse effects observed during MRI or clinical examinations.

This method, which combines pulsed ultrasound with systemic microbubble injection, effectively increases drug delivery to the brain and has the potential to enhance the efficacy of chemotherapy treatments like carboplatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Carpentier, A., Canney, M., Vignot, A., et al.[2017]

A Phase I clinical trial involving 10 patients with recurrent high-grade gliomas demonstrated that intracerebral convection-enhanced delivery (CED) of carboplatin is feasible and safe at doses up to 4μg over 72 hours, with only one possible adverse event reported.

The median progression-free survival (PFS) and overall survival (OS) after treatment were 2.1 months and 9.6 months, respectively, indicating that while the treatment is safe, further studies are needed to assess its efficacy in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of intracerebral convection-enhanced delivery of carboplatin for treatment of recurrent high-grade gliomas. Wang, JL., Barth, RF., Cavaliere, R., et al.[2021]

The study demonstrates the successful use of a novel implantable convection-enhanced delivery (CED) system for carboplatin in a patient with recurrent glioblastoma, showing precise catheter placement and well-tolerated drug infusions.

Follow-up MRI results indicated a significant reduction in tumor volume from 42.6 ml to 24.6 ml after treatment, suggesting that CED of carboplatin may improve clinical outcomes for glioblastoma patients by effectively bypassing the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel implantable catheter system with transcutaneous port for intermittent convection-enhanced delivery of carboplatin for recurrent glioblastoma. Barua, NU., Hopkins, K., Woolley, M., et al.[2022]

Using focused ultrasound (FUS) to disrupt the blood-brain barrier (BBB) in rats allowed for significantly enhanced delivery of carboplatin to brain tumors, increasing drug concentrations in tumor tissue by up to 7.3 times without causing neurotoxicity.

Rats treated with FUS and carboplatin showed a 96% increase in tumor volume doubling time and a 48% increase in median survival compared to those receiving carboplatin alone, indicating a promising approach for improving treatment outcomes in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acoustic feedback enables safe and reliable carboplatin delivery across the blood-brain barrier with a clinical focused ultrasound system and improves survival in a rat glioma model. McDannold, N., Zhang, Y., Supko, JG., et al.[2020]

Low-intensity pulsed ultrasound (LIPU) significantly enhances the delivery of paclitaxel across the blood-brain barrier, increasing drug concentration in the brain by 3- to 5-fold, which improves treatment efficacy for glioma.

Among the two formulations tested, albumin-bound paclitaxel (ABX) not only extended survival in glioma models but also showed better tolerability compared to paclitaxel dissolved in cremophor (CrEL-PTX), making ABX the preferred option for future clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations. Zhang, DY., Dmello, C., Chen, L., et al.[2021]

In a clinical trial involving 21 patients with recurrent glioblastoma, the use of the SonoCloud-1 device to transiently disrupt the blood-brain barrier (BBB) before chemotherapy with carboplatin was well tolerated, with only manageable and transient side effects observed.

Patients who experienced clear BBB disruption had significantly better outcomes, with a median progression-free survival of 4.11 months and overall survival of 12.94 months, compared to those with poor disruption, highlighting the potential of LIPU to enhance drug delivery in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma. Idbaih, A., Canney, M., Belin, L., et al.[2019]

Using ultrasound to open the blood-brain barrier significantly increased the concentration of carboplatin in brain tissue by 5.2 times in the targeted area, suggesting a more effective delivery method for treating glioblastoma.

This method of enhancing drug delivery is currently being evaluated in a phase 1 clinical trial, indicating its potential as a promising approach for improving treatment outcomes in patients with aggressive brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Goldwirt, L., Canney, M., Horodyckid, C., et al.[2016]

Combining carboplatin chemotherapy with ultrasound-induced blood-brain barrier opening (US-BBB) significantly improved survival and delayed tumor growth in mouse models of glioblastoma, with a 4.2-fold increase in drug penetration into the brain.

The treatment showed no significant neurological or systemic toxicity, suggesting that US-BBB could be a safe and effective method to enhance the delivery of chemotherapy for glioblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temporary blood-brain barrier disruption by low intensity pulsed ultrasound increases carboplatin delivery and efficacy in preclinical models of glioblastoma. Dréan, A., Lemaire, N., Bouchoux, G., et al.[2020]

A phase I dose-escalation study is being conducted to evaluate the safety and maximum tolerated dose of carboplatin delivered directly into the brain using convection-enhanced delivery (CED) in patients with recurrent glioblastoma multiforme (GBM), involving 18 patients divided into 6 cohorts.

Carboplatin is chosen for this method because glioblastoma cells are sensitive to it at non-toxic levels for normal brain tissue, potentially improving treatment efficacy while minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of carboplatin administered by convection-enhanced delivery to patients with recurrent/progressive glioblastoma multiforme. White, E., Bienemann, A., Taylor, H., et al.[2021]

In a study of 56 patients with newly diagnosed glioblastoma, treatment with radiotherapy and concurrent carboplatin plus teniposide followed by carmustine resulted in a median survival time of 12.5 months and a time to progression of 7.5 months.

The treatment was generally well-tolerated, with acceptable levels of toxicity, although 7.1% of patients experienced radiation necrosis, indicating that while the regimen is effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and teniposide concurrent with radiotherapy in patients with glioblastoma multiforme: a phase II study. Brandes, AA., Rigon, A., Zampieri, P., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05902169

Study Details | NCT05902169 | Sonocloud-9 in Association ... 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 ...

2. fusfoundation.org fusfoundation.org/posts/recurrent-glioblastoma-clinical-trial-results-of-sonocloud-9-plus-chemotherapy/

Recurrent Glioblastoma Clinical Trial Results of ... All but one case of blurred vision resolved within 15 minutes after the treatment ended. Regarding whether to give the carboplatin before or ...

3. nature.com nature.com/articles/s41467-024-45818-7

Repeated blood–brain barrier opening with a nine-emitter ... This trial was designed to evaluate the safety of concomitant carboplatin administration with transient disruption of the blood–brain barrier by ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9443390/

OS07.3.A Phase 1/2 clinical trial of blood-brain barrier ... ... (SonoCloud-9) in patients with recurrent glioblastoma receiving carboplatin chemotherapy. ... Updated and mature outcome results will be presented.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10766

Sonocloud-9 in Association With Carboplatin Versus ... 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 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03744026

Study Details | NCT03744026 | Safety and Efficacy of ... 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 ...

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05902169

Sonocloud-9 in Association With Carboplatin Versus Standard ... 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 ...