Clinical Trials /

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

NCT04528680

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 after completion of the 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 followed by sonication (= procedure of activating ultrasound and opening the BBB) and tissue concentrations in different parts of the resected tumor will be measured. 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.

Related Conditions:
  • Glioblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
Chemotherapy, albumin-bound paclitaxelAbraxane®, ABXSC9/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 after completion of the 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 followed by sonication (= procedure of activating ultrasound and opening the BBB) and tissue concentrations in different parts of the resected tumor will be measured. 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. 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

NameTypeDescriptionInterventions
SC9/ABXExperimentalInfusion 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:Not yet recruiting
Lead Sponsor:Northwestern University

Trial Keywords

  • ultrasound
  • SonoCloud
  • blood-brain barrier
  • paclitaxel
  • albumin-bound paclitaxel
  • Abraxane®

Last Updated

August 26, 2020