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

• Status: Recruiting
• Trial end date: 2025-09-01
• Target enrollment: 0
• Participant gender: All

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 this phase 1 trial increasing doses of chemotherapy will be delivered as long deemed safe and prior patient had not experienced severe toxicity. Once the the recommended dosing has been established, 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 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 will occur immediately after the test dose of chemotherapy is administered.

The objectives of this trial are to establish a safe and effective dose of ABX, 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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Collaborators: Bristol-Myers Squibb; CarThera; Lantheus Medical Imaging
• Treatments: Albumin-Bound Paclitaxel; Paclitaxel

Criteria

Inclusion Criteria:

1. Confirmed diagnosis of Isocitrate Dehydrogenase 1 (IDH1) wild-type glioblastoma on pathology from initial surgery (e.g. IDH R132H neg)

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. Stable or decreasing dose of corticosteroids equivalent to ≤ 6 mg dexamethasone, for ≥ 7 days prior to registration

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 nab-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

7. Medical contraindications to Abraxane®

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.