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Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel for Recurrent Glioblastoma (SC9/ABX)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04528680
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : October 12, 2020
Bristol-Myers Squibb
Lantheus Medical Imaging
Information provided by (Responsible Party):
Adam Sonabend, Northwestern University

Brief 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.

Condition or disease Intervention/treatment Phase
Glioblastoma Gliosarcoma GBM Glioblastoma Multiforme Glioblastoma, IDH-wildtype Recurrent Glioblastoma Device: Sonication for opening of blood-brain barrier Drug: Chemotherapy, albumin-bound paclitaxel Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : October 2020
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ultrasound
Drug Information available for: Paclitaxel

Arm Intervention/treatment
Experimental: SC9/ABX
Infusion of albumin-bound paclitaxel immediately followed by sonication using the SC9 device and microbubbles in order to open the blood-brain barrier.
Device: Sonication for opening of blood-brain barrier
Implantation of SC-9 device and repeat activation of 9 ultrasound emitters during i.v. injection of microbubbles
Other Name: SonoCloud-9 device, SC-9

Drug: Chemotherapy, albumin-bound paclitaxel
Intravenous infusion of ABX over 30 minutes
Other Names:
  • Abraxane®
  • ABX

Primary Outcome Measures :
  1. Dose limiting toxicity [ Time Frame: 1st treatment cycle = 3 weeks ]
    Occurrence of ≥ grade 3 treatment related toxicity

  2. 1-year survival rate [ Time Frame: 12-months ]
    Survival time from date of tumor resection and device implantation

Secondary Outcome Measures :
  1. Incidence of side effects/toxicity associated with Sonication/ABX treatment [ Time Frame: 12 months ]
    Safety and tolerance

Other Outcome Measures:
  1. Extent of tumor and peritumoral tissue covered by BBB opening [ Time Frame: 1st cycle (cycle = 3 weeks) ]
    increase in Gd contrast enhancement post sonication

  2. Objective response rate (RANO) [ Time Frame: 6 months ]
    measurement of tumor shrinkage (if there is residual disease)

  3. Measurement of circulating tumor DNA, methods and units for this measure are to be determined and still under evaluation. [ Time Frame: 1st cycle, cycles 2 - 6 as applicable (cycle = 3 weeks) ]
    compare before and after sonication

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04528680

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Contact: Christina Amidei, APN, PhD (312) 695-9124
Contact: Roger Stupp, MD

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United States, Illinois
Northwestern Memorial Hospital Recruiting
Chicago, Illinois, United States, 60611
Contact: Shanna Davis, BSN, RN    312-926-9441   
Contact: Christina Amidei, PhD, APN    (312) 695-9124   
Principal Investigator: Adam M Sonabend, MD         
Principal Investigator: Roger Stupp, MD         
Sub-Investigator: Karan Dixit, MD         
Sub-Investigator: Priya Kumthekar, MD         
Sub-Investigator: Rimas V Lukas, MD         
Sponsors and Collaborators
Northwestern University
Bristol-Myers Squibb
Lantheus Medical Imaging
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Study Chair: Roger Stupp, MD Northwestern University
Principal Investigator: Adam M Sonabend, MD Northwestern University
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Responsible Party: Adam Sonabend, Assistant Professor, Feinberg School of Medicine, Neurological Surgery, Northwestern University Identifier: NCT04528680    
Other Study ID Numbers: NU 20C03
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: October 12, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by Adam Sonabend, Northwestern University:
blood-brain barrier
albumin-bound paclitaxel
Additional relevant MeSH terms:
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Albumin-Bound Paclitaxel
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action