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

Summary

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.

Conditions

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

Interventions

DEVICE

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

DRUG

Chemotherapy, albumin-bound paclitaxel

Intravenous infusion of ABX over 30 minutes

DRUG

Chemotherapy, carboplatin

Intravenous infusion of carboplatin over 30 minutes

Sponsors & Collaborators

• Northwestern University

  lead OTHER

• CarThera

  collaborator INDUSTRY

• Bristol-Myers Squibb

  collaborator INDUSTRY

• National Cancer Institute (NCI)

  collaborator NIH

Principal Investigators

• Roger Stupp, MD · Northwestern University

• Adam M Sonabend, MD · Northwestern University

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-10-29

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations