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

  • STATUS
    Recruiting
  • End date
    Sep 25, 2025
  • participants needed
    39
  • sponsor
    Northwestern University
Updated on 25 January 2021
corticosteroids
karnofsky performance status
dexamethasone
glioblastoma multiforme
recurrent glioblastoma
contrast-enhanced magnetic resonance imaging
recurrent tumor

Summary

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.

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.

Details
Condition Glioma, gliosarcoma, Glioblastoma Multiforme, Glomerular Basement Membrane, Recurrent Glioblastoma, Gliomas, Glioblastoma, IDH-wildtype, Glioblastoma, IDH-wildtype, glioblastoma, Glioblastoma, IDH-wildtype
Treatment Sonication for opening of blood-brain barrier, Chemotherapy, albumin-bound paclitaxel
Clinical Study IdentifierNCT04528680
SponsorNorthwestern University
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Confirmed diagnosis of Isocitrate Dehydrogenase 1 (IDH1) wild-type glioblastoma on pathology from initial surgery (e.g. IDH R132H neg)
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 1cm) on MRI
Non-measurable/evaluable: contrast-enhancement diameters < 1 cm
Maximal tumor diameter pre-surgery 70 mm on T1wMRI
Candidate for at least partial surgical resection
Greater 12 weeks from completion of radiation therapy
Age 18 years
Stable or decreasing dose of corticosteroids equivalent to 6 mg dexamethasone, for 7 days prior to registration
WHO performance status 2 (equivalent to Karnofsky Performance Status (KPS) of 70)
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 nab-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

Exclusion Criteria

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 antiepileptics
Have clinical evidence of peripheral neuropathy on examination
Have received any other investigational 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
Medical contraindications to Abraxane
Have an uncontrolled intercurrent illness
Are pregnant or nursing
Have a 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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note