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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

57 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-29

Study Completion Date

2025-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

NCT05864534

Newly Diagnosed Glioblastoma Glioblastoma, Isocitric Dehydrogenase (IDH)-Wildtype Gliosarcoma +1 more

RECRUITING PHASE2

Safety of BBB Opening With the SonoCloud

NCT02253212

Glioblastoma Glioma Brain Tumor

COMPLETED PHASE1/PHASE2

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

NCT03744026

Glioblastoma, Adult

COMPLETED PHASE1/PHASE2

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 Tumor Malignant Glioma Embryonal Tumor

RECRUITING PHASE1

Pembrolizumab in Treating Patients With Recurrent Glioblastoma

NCT02337686

Recurrent Glioblastoma Recurrent Gliosarcoma

ACTIVE_NOT_RECRUITING PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Glioblastoma Gliosarcoma GBM Glioblastoma Multiforme Glioblastoma, IDH-wildtype Recurrent Glioblastoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

SC9/ABX (phase 1); SC9/ABX/Carboplatin (phase 2)

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.

Group Type EXPERIMENTAL

Sonication for opening of blood-brain barrier

Intervention Type DEVICE

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

Chemotherapy, albumin-bound paclitaxel

Intervention Type DRUG

Intravenous infusion of ABX over 30 minutes

Chemotherapy, carboplatin

Intervention Type DRUG

Intravenous infusion of carboplatin over 30 minutes

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Sonication for opening of blood-brain barrier

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

Intervention Type DEVICE

Chemotherapy, albumin-bound paclitaxel

Intravenous infusion of ABX over 30 minutes

Intervention Type DRUG

Chemotherapy, carboplatin

Intravenous infusion of carboplatin over 30 minutes

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

SonoCloud-9 device, SC-9 Abraxane® ABX Paraplatin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Confirmed diagnosis of Isocitrate Dehydrogenase 1 (IDH1) wild-type glioblastoma on pathology from initial surgery (e.g. IDH R132H neg); morphologic or molecular determination of grade 4
2. Ability to undergo contrast-enhanced MRI
3. Radiographic evidence of tumor recurrence/progression after failure of 1 - 2 lines of prior therapy
4. Measurable or evaluable disease

1. Measurable: contrast-enhancement (bidirectional diameters ≥ 1cm) on MRI
2. Non-measurable/evaluable: contrast-enhancement diameters \< 1 cm
5. Maximal tumor diameter pre-surgery ≤ 70 mm on T1wMRI
6. Candidate for at least partial surgical resection
7. Greater 12 weeks from completion of radiation therapy
8. Age ≥ 18 years
9. If receiving dexamethasone for mass effect, a stable daily dose of dexamethasone at \< 6 mg within 7 days of registration, or if dexamethasone dose is decreasing, average daily dose of \< 6 mg in the 7 days prior to registration. Patients on dexamethasone for reasons other than mass effect may still be enrolled.
10. WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) of ≥70)
11. Adequate hepatic, renal and bone marrow function, documented with normal laboratory values or no more than grade 1 outside the norm performed within 14 days prior to registration
12. For patients with a childbearing potential

1. Negative pregnancy test within 14 days prior to registration
2. Agreement to use adequate contraception for the duration of study participation, and for 3 and 6 months after the last dose of albumin-bound paclitaxel for men and women of childbearing potential, respectively.
13. Have the ability to understand and the willingness to sign a written informed consent prior to registration on study
14. Be willing and able to comply with the protocol for the duration of the study
15. Provide written, signed and dated informed consent prior to study registration. NOTE: no study-specific screening procedures may be performed until written consent has been obtained

Exclusion Criteria

1. Have multifocal disease that cannot be encompassed in the ultrasound fields:

1. e.g. \> 70-mm apart
2. tumor located in the posterior fossa
2. Patients at risk of cranial wound dehiscence
3. Have uncontrolled epilepsy or require treatment with enzyme-inducing antiepileptics
4. Have clinical evidence of peripheral neuropathy on examination
5. Have received any other investigational agents within 4 weeks of registration
6. Have received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel or carboplatin
7. Medical contraindications to Abraxane® or carboplatin
8. Have an uncontrolled intercurrent illness
9. Are pregnant or nursing
10. Have a history of active malignancy within 3 years prior to registration.
11. Have a known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in Definity® (the FDA-approved ultrasound contrast agent to be used in this study)
12. Patients with coils, clips, shunts, intravascular stents, and/or non-removable wafer, non resorbable dura substitute, or reservoirs.
13. Patients with medical need to continue antiplatelet therapy.
14. Patients with known significant cardiac disease, known to have right-to-left shunts, severe pulmonary hypertension (pulmonary artery pressure \> 90 mmHg), uncontrolled systemic hypertension, or adult respiratory distress syndrome (patient at risk for microbubble reaction).
15. Patients with impaired thermo-regulation or temperature sensation (due to device)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No