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

Who is this study for? Patients with Glioblastoma
What treatments are being studied? Sonication for Opening of Blood-Brain Barrier+Chemotherapy, Albumin-Bound Paclitaxel
Status: Recruiting
Location: See location...
Intervention Type: Drug, Device
Study Type: Interventional
Study Phase: Phase 1/Phase 2

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.

Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No

• 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

• Ability to undergo contrast-enhanced MRI

• Radiographic evidence of tumor recurrence/progression after failure of 1 - 2 lines of prior therapy

• Measurable or evaluable disease

• Measurable: contrast-enhancement (bidirectional diameters ≥ 1cm) on MRI

• Non-measurable/evaluable: contrast-enhancement diameters < 1 cm

• Maximal tumor diameter pre-surgery ≤ 70 mm on T1wMRI

• Candidate for at least partial surgical resection

• Greater 12 weeks from completion of radiation therapy

• Age ≥ 18 years

• 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.

• WHO performance status ≤ 2 (equivalent to Karnofsky Performance Status (KPS) of ≥70)

• 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

• For patients with a childbearing potential

• Negative pregnancy test within 14 days prior to registration

• 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.

• Have the ability to understand and the willingness to sign a written informed consent prior to registration on study

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

• 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

United States
Northwestern Memorial Hospital
Contact Information
Christina Amidei, APN, PhD
(312) 695-9124
Roger Stupp, MD
Time Frame
Start Date: October 29, 2020
Estimated Completion Date: September 2025
Target number of participants: 57
Experimental: 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.
Collaborators: CarThera, Lantheus Medical Imaging, Bristol-Myers Squibb
Leads: Northwestern University

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