Human stem cell-derived neurons

Phase I/II 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


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.

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 ≥ 1 cm) or MRI.
    2. Non-measurable/evaluable: contrast-enhancement diameters less than 1 cm.
  5. Maximal tumor diameter pre-surgery ≤ 70 mm on T1wMRI.
  6. Candidate for at least partial surgical resection.
  7. More than 12 weeks from completion of radiation therapy.
  8. Age ≥ 18 years.
  9. 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.
  10. WHO performance status of ≤ 2 (equivalent to Karnofsky Performance Status (KPS) of ≥70).
  11. 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.
  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 anti epileptics.
  4. Have clinical evidence of peripheral neuropathy on examination.
  5. Have received any other investigation 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 known 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).

Stay Informed