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

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ClinicalTrials.gov Identifier: NCT04528680
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : October 12, 2020
Sponsor:
Collaborators:
CarThera
Bristol-Myers Squibb
Lantheus Medical Imaging
Information provided by (Responsible Party):
Adam Sonabend, Northwestern University

Tracking Information
First Submitted Date  ICMJE August 24, 2020
First Posted Date  ICMJE August 27, 2020
Last Update Posted Date October 12, 2020
Estimated Study Start Date  ICMJE October 2020
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
  • Dose limiting toxicity [ Time Frame: 1st treatment cycle = 3 weeks ]
    Occurrence of ≥ grade 3 treatment related toxicity
  • 1-year survival rate [ Time Frame: 12-months ]
    Survival time from date of tumor resection and device implantation
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 26, 2020)
Incidence of side effects/toxicity associated with Sonication/ABX treatment [ Time Frame: 12 months ]
Safety and tolerance
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 8, 2020)
  • Extent of tumor and peritumoral tissue covered by BBB opening [ Time Frame: 1st cycle (cycle = 3 weeks) ]
    increase in Gd contrast enhancement post sonication
  • Objective response rate (RANO) [ Time Frame: 6 months ]
    measurement of tumor shrinkage (if there is residual disease)
  • 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
Original Other Pre-specified Outcome Measures
 (submitted: August 26, 2020)
  • Extent of tumor and peritumoral tissue covered by BBB opening [ Time Frame: 1st cycle (cycle = 3 weeks) ]
    increase in Gd contrast enhancement post sonication
  • Objective response rate (RANO) [ Time Frame: 6 months ]
    measurement of tumor shrinkage (if there is residual disease)
  • Measurement of circulation tumor DNA [ Time Frame: 1st cycle, cycles 2 - 6 as applicable (cycle = 3 weeks) ]
    compare before and after sonication
 
Descriptive Information
Brief Title  ICMJE Ultrasound-based Blood-brain Barrier Opening and Albumin-bound Paclitaxel for Recurrent Glioblastoma
Official Title  ICMJE 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
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.

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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma
  • Gliosarcoma
  • GBM
  • Glioblastoma Multiforme
  • Glioblastoma, IDH-wildtype
  • Recurrent Glioblastoma
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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.
Interventions:
  • Device: Sonication for opening of blood-brain barrier
  • Drug: Chemotherapy, albumin-bound paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 8, 2020)
39
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2020)
37
Estimated Study Completion Date  ICMJE September 2025
Estimated Primary Completion Date August 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Christina Amidei, APN, PhD (312) 695-9124 christina.amidei@nm.org
Contact: Roger Stupp, MD roger.stupp@northwestern.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04528680
Other Study ID Numbers  ICMJE NU 20C03
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Adam Sonabend, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE
  • CarThera
  • Bristol-Myers Squibb
  • Lantheus Medical Imaging
Investigators  ICMJE
Study Chair: Roger Stupp, MD Northwestern University
Principal Investigator: Adam M Sonabend, MD Northwestern University
PRS Account Northwestern University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP