Ultrasound-assisted Chemotherapy for Glioblastoma

(SC9/ABX Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Adam M Sonabend, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Northwestern University

Must not be taking: Enzyme-inducing antiepileptics

Disqualifiers: Uncontrolled epilepsy, Peripheral neuropathy, Active malignancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on enzyme-inducing antiepileptics or need to continue antiplatelet therapy, you may not be eligible to participate.

What data supports the effectiveness of the treatment for glioblastoma?

Research shows that using ultrasound to open the blood-brain barrier can increase the concentration of carboplatin in brain tissue, potentially improving its effectiveness against glioblastoma. Additionally, carboplatin has shown some effectiveness in glioblastoma when used before radiation therapy, with a median survival of 19.2 months. ^{1 2 3 4 5}

Is the combination of paclitaxel and carboplatin generally safe for humans?

The combination of paclitaxel and carboplatin has been studied in various cancers, showing that it is generally well tolerated. Common side effects include low blood cell counts, hair loss, mild muscle pain, and fatigue, with some rare cases of severe allergic reactions. ^{6 7 8 9 10}

What makes ultrasound-assisted chemotherapy for glioblastoma unique?

This treatment uses ultrasound to temporarily open the blood-brain barrier, allowing higher concentrations of chemotherapy drugs like carboplatin and paclitaxel to reach the brain, which is not possible with standard intravenous delivery. ^{2 11 12 13 14}

Research Team

Roger Stupp, MD

Principal Investigator

Northwestern University

Adam M Sonabend, MD

Principal Investigator

Northwestern University

Eligibility Criteria

Adults over 18 with a specific type of brain cancer called IDH1 wild-type glioblastoma, who are fit for surgery and have had up to two prior treatments. They must not be pregnant, agree to use contraception, and have stable vital organ functions. Excluded are those with uncontrolled epilepsy, certain allergies or medical conditions that conflict with the trial's procedures.

Inclusion Criteria

It has been over 12 weeks since I finished my radiation therapy.

For patients with a childbearing potential

Be willing and able to comply with the protocol for the duration of the study

Exclusion Criteria

Have an uncontrolled intercurrent illness

Have clinical evidence of peripheral neuropathy on examination

I cannot take Abraxane or carboplatin due to health reasons.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Resection and Device Implantation

Eligible patients undergo craniotomy for tumor resection and implantation of the sonication device. A test dose of chemotherapy may be administered.

1 day

1 visit (in-person)

Phase 1 Treatment

Sonication and administration of albumin-bound paclitaxel every 3 weeks to establish a safe dose. Blood samples collected for circulating tumor DNA.

Until disease progression

Every 3 weeks (in-person)

Phase 2 Treatment

Addition of carboplatin to the regimen with sonication and albumin-bound paclitaxel administration every 3 weeks.

Until disease progression

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

12 months

Treatment Details

Interventions

• Carboplatin (Alkylating agents)
• Paclitaxel (Anti-tumor antibiotic)
• Sonication for opening of blood-brain barrier (Procedure)

Trial Overview The trial tests if using ultrasound to open the blood-brain barrier before giving chemotherapy (albumin-bound paclitaxel followed by carboplatin) can safely improve treatment outcomes in recurrent glioblastoma patients. The study will determine safe dosages and measure how well this method delivers chemo into the tumor.

Participant Groups

Group I: SC9/ABX (phase 1); SC9/ABX/Carboplatin (phase 2) Experimental Treatment 3 Interventions

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.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Northwestern Memorial Hospital Chicago, IL

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1674

Patients Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14080

Patients Recruited

41,180,000+

CarThera

Industry Sponsor

Trials

6

Patients Recruited

710+

Bristol-Myers Squibb

Industry Sponsor

Trials

2731

Patients Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Lantheus Medical Imaging

Industry Sponsor

Trials

57

Patients Recruited

4,333,000+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. Boiardi, A., Silvani, A., Milanesi, I., et al.[2019]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. Schuette, W., Blankenburg, T., Guschall, W., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The added value of bevacizumab concomitantly administered with carboplatin versus carboplatin alone in patients with recurrent glioblastomas. Kaloshi, G., Diamandi, P., Cakani, B., et al.[2017]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin chemotherapy before irradiation in newly diagnosed glioblastoma multiforme. Gruber, ML., Glass, J., Choudhri, H., et al.[2019]

A phase I trial showed that carboplatin and paclitaxel can be safely combined at full doses for treating advanced ovarian cancer, indicating acceptable toxicity levels for patients.

The combination therapy is moving forward to larger randomized trials to compare its effectiveness against cisplatin plus paclitaxel, with specific dosing strategies planned for optimal treatment cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel in ovarian cancer. Ozols, RF.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary results of two dose-finding studies of paclitaxel (Taxol) and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. Giaccone, G., Huizing, M., ten Bokkel Huinink, W., et al.[2015]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. Ratanatharathorn, V., Jirajarus, M., Sirachainan, E., et al.[2015]

In a phase II trial involving 31 patients with nonoperable stage III and IV non-small cell lung cancer (NSCLC), the combination of paclitaxel and carboplatin showed promising efficacy, with 33% of evaluable patients achieving a partial response and 48% having stable disease.

The treatment was generally well tolerated, with manageable side effects; however, 10.7% of patients experienced grade 2/3 neutropenia, and there was one reported death due to a severe allergic reaction, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in nonoperable non-small cell lung cancer. Kosmidis, P., Mylonakis, N., Fountzilas, G., et al.[2015]

In a multicenter phase II study involving 50 patients with advanced ovarian cancer who had previously undergone platinum-based chemotherapy, the combination of paclitaxel and carboplatin showed an overall response rate of 43%, indicating its efficacy in this patient population.

The treatment was generally safe, with myelosuppression being the most common severe side effect, but only one case of neutropenic fever was reported, suggesting that this regimen can be administered safely to outpatients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study. Pujade-Lauraine, E., Guastalla, JP., Weber, B., et al.[2015]

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]

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]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial. Sonabend, AM., Gould, A., Amidei, C., et al.[2023]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma. Chen, H., Zhang, S., Fang, Q., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Multicenter randomized trial for stage IIIB/IV non-small-cell lung cancer using every-3-week versus weekly paclitaxel/carboplatin. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

The added value of bevacizumab concomitantly administered with carboplatin versus carboplatin alone in patients with recurrent glioblastomas. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Carboplatin chemotherapy before irradiation in newly diagnosed glioblastoma multiforme. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel in ovarian cancer. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Preliminary results of two dose-finding studies of paclitaxel (Taxol) and carboplatin in non-small cell lung and ovarian cancers: a European Cancer Centre effort. [2015]

8. Thailand pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Paclitaxel and carboplatin in nonoperable non-small cell lung cancer. [2015]

10. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study. [2015]

11. United States 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial. [2023]

14. United States pubmed.ncbi.nlm.nih.gov

Biomimetic Nanosonosensitizers Combined with Noninvasive Ultrasound Actuation to Reverse Drug Resistance and Sonodynamic-Enhanced Chemotherapy against Orthotopic Glioblastoma. [2023]