Description:
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.
Title
- Brief Title: Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel for Recurrent Glioblastoma
- Official Title: Phase 1 / 2 Trial of Blood-brain Barrier Opening With an Implantable Ultrasound Device SonoCloud-9 and Treatment With Albumin-bound Paclitaxel in Patients With Recurrent Glioblastoma
Clinical Trial IDs
- ORG STUDY ID:
NU 20C03
- NCT ID:
NCT04528680
Conditions
- Glioblastoma
- Gliosarcoma
- GBM
- Glioblastoma Multiforme
- Glioblastoma, IDH-wildtype
- Recurrent Glioblastoma
Interventions
Drug | Synonyms | Arms |
---|
Chemotherapy, albumin-bound paclitaxel | Abraxane®, ABX | SC9/ABX |
Purpose
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.
Detailed Description
Eligible patients will undergo craniotomy for tumor resection. During the tumor resection, an
initial low dose of paclitaxel will be given following sonication. In select patients, the
sonication procedure will occur immediately after the test dose of chemotherapy is
administered.The sonication device will be implanted at the end of the procedure. About two
weeks after surgery, patients will undergo sonication and albumin-bound paclitaxel
administration with MRI to quantify extent of blood brain barrier opening. Sonication and
administration of albumin-bound paclitaxel will continue every 3 weeks until disease
progression. The planned ABX starting dose is 40 mg/m2 of ABX, to be escalated in the absence
of significant toxicity up to 260 mg/m2. Blood samples for circulating tumor DNA will also be
collected before and after each sonication.
Trial Arms
Name | Type | Description | Interventions |
---|
SC9/ABX | Experimental | Infusion of albumin-bound paclitaxel immediately followed by sonication using the SC9 device and microbubbles in order to open the blood-brain barrier. | - Chemotherapy, albumin-bound paclitaxel
|
Eligibility 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose limiting toxicity |
Time Frame: | 1st treatment cycle = 3 weeks |
Safety Issue: | |
Description: | Occurrence of ≥ grade 3 treatment related toxicity |
Secondary Outcome Measures
Measure: | Incidence of side effects/toxicity associated with Sonication/ABX treatment |
Time Frame: | 12 months |
Safety Issue: | |
Description: | Safety and tolerance |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Northwestern University |
Trial Keywords
- ultrasound
- SonoCloud
- blood-brain barrier
- paclitaxel
- albumin-bound paclitaxel
- Abraxane®
Last Updated
October 12, 2020