Phase I/II Trial of Blood-Brain Barrier Opening With an Implantable Ultrasound Device SonoCloud-9 and Treatment With Albumin-bound Paclitaxel in Patients With Recurrent Glioblastoma
This is a phase I/II trial that aims to to establish a safe and effective dose of albumin-bound paclitaxel, to demonstrate that the opening of the blood-brain barrier increases chemotherapy concentration in the tumor, and to estimate how effective this treatment is in reducing the tumor burden and prolonging life.
Paclitaxel is a chemotherapy medication used to treat other types of cancer, including ovarian cancer, non-small cell lung cancer, and Kaposi sarcoma. Although paclitaxel is one of the most active agents against glioblastoma in preclinical models, the blood-brain barrier (BBB) has limited the drug's use in clinical setting. This trial will use a novel device with nine ultrasound emitters implanted at the time of surgical resection of the recurrent tumor, allowing a temporary opening the BBB immediately prior to chemotherapy infusion with albumin-bound paclitaxel.
- 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 ≥ 1 cm) or MRI.
- Non-measurable/evaluable: contrast-enhancement diameters less than 1 cm.
- Maximal tumor diameter pre-surgery ≤ 70 mm on T1wMRI.
- Candidate for at least partial surgical resection.
- More than 12 weeks from completion of radiation therapy.
- Age ≥ 18 years.
- If receiving dexamethasone for mass effect, a stable dose of dexamethasone at less than 6 mg within 7 days of registration, or if dexamethasone dose is decreasing, average daily dose of less than 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 of ≤ 2 (equivalent to Karnofsky Performance Status (KPS) of ≥70).
- 1 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.
- Have multifocal disease that cannot be encompassed in the ultrasound fields:
- e.g. >70-mm apart
- tumor located in the posterior fossa
- Patients at risk of cranial wound dehiscence.
- Have uncontrolled epilepsy or require treatment with enzyme-inducing anti epileptics.
- Have clinical evidence of peripheral neuropathy on examination.
- Have received any other investigation agents within 4 weeks of registration.
- Have received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel or carboplatin.
- Medical contraindications to Abraxane® or carboplatin.
- Have an uncontrolled intercurrent illness.
- Are pregnant or nursing.
- Have a known history of active malignancy within 3 years prior to registration.
- 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).
- Patients with coils, clips, shunts, intravascular stents, and/or non-removable wafer, non resorbable dura substitute, or reservoirs.
- Patients with medical need to continue antiplatelet therapy.
- 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).
- Patients with impaired thermo-regulation or temperature sensation (due to device).