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.
Name: Sonication for opening of blood-brain barrier
Name: Chemotherapy, albumin-bound paclitaxel
Description: Occurrence of ≥ grade 3 treatment related toxicity
Measure: Dose limiting toxicity Time: 1st treatment cycle = 3 weeksDescription: Survival time from date of tumor resection and device implantation
Measure: 1-year survival rate Time: 12-monthsDescription: Safety and tolerance
Measure: Incidence of side effects/toxicity associated with Sonication/ABX treatment Time: 12 monthsDescription: increase in Gd contrast enhancement post sonication
Measure: Extent of tumor and peritumoral tissue covered by BBB opening Time: 1st cycle (cycle = 3 weeks)Description: measurement of tumor shrinkage (if there is residual disease)
Measure: Objective response rate (RANO) Time: 6 monthsDescription: compare before and after sonication
Measure: Measurement of circulating tumor DNA, methods and units for this measure are to be determined and still under evaluation. Time: 1st cycle, cycles 2 - 6 as applicable (cycle = 3 weeks)Allocation: N/A
Single Group Assignment
There is one SNP
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. --- R132H ---