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

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)