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Trial record 1 of 1 for:    Sonabend | Glioblastoma | United States
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Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel and Carboplatin 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 : May 26, 2023
Bristol-Myers Squibb
Lantheus Medical Imaging
Information provided by (Responsible Party):
Adam M 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 the phase 1 component, increasing doses of chemotherapy will be delivered as long deemed safe based on the prior patient not experiencing severe toxicity. Once the the recommended dosing has been established, carboplatin will be added to the regimen and 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 and when feasible, 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 may occur immediately after the test dose of chemotherapy is administered.

The objectives of this trial are to establish a safe and effective dose of albumin-bound paclitaxel, 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 Drug: Chemotherapy, carboplatin Phase 1 Phase 2

Detailed Description:
Eligible patients will undergo craniotomy for tumor resection. During the tumor resection and when possible, an initial low dose of albumin-bound paclitaxel will be given following sonication. In select patients, the sonication procedure may occur immediately after the test dose of chemotherapy is administered. The sonication device will be implanted at the end of the procedure. In phase 1, 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 albumin-bound paclitaxel starting dose is 40 mg/m2, 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. In phase 2, pre-sonication carboplatin at AUC 5 will be added to the regimen, with a safety run-in for the first 6 patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 57 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 and Carboplatin in Patients With Recurrent Glioblastoma
Actual Study Start Date : October 29, 2020
Estimated Primary Completion Date : September 10, 2024
Estimated Study Completion Date : September 2025

Arm Intervention/treatment
Experimental: SC9/ABX (phase 1); SC9/ABX/Carboplatin (phase 2)
Infusion of albumin-bound paclitaxel immediately followed by sonication using the SC9 device and microbubbles in order to open the blood-brain barrier in phase 1. In phase 2, patients will receive carboplatin immediately prior to sonication using the SC9 device and microbubbles in order to open the blood-brain barrier, then will receive albumin-bound paclitaxel upon completion of sonication.
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

Drug: Chemotherapy, carboplatin
Intravenous infusion of carboplatin over 30 minutes
Other Name: Paraplatin

Primary Outcome Measures :
  1. Dose limiting toxicity (Phase1) [ Time Frame: 1st treatment cycle = 3 weeks ]
    Occurrence of ≥ grade 3 treatment related toxicity

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

  3. Relationship between overall survival and SSR3 (Phase 2) [ Time Frame: through study completion, an average of 2 years ]
    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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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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); 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 ≥ 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. If receiving dexamethasone for mass effect, a stable daily dose of dexamethasone at < 6 mg within 7 days of registration, or if dexamethasone dose is decreasing, average daily dose of < 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 ≤ 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 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 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 or carboplatin
  7. Medical contraindications to Abraxane® or carboplatin
  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.
  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)

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: 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
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Adam M 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: May 26, 2023
Last Verified: May 2023
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 M Sonabend, Northwestern University:
blood-brain barrier
albumin-bound paclitaxel
Additional relevant MeSH terms:
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Disease Attributes
Pathologic Processes
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action