Safety of BBB Opening With the SonoCloud

NCT02253212 | Completed Phase 1 DMC

• 2 other identifiers: P1209052014-000393-19
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

PURPOSE: The purpose of this study is to determine whether transient opening of the blood-brain barrier by pulsed ultrasound using the SonoCloud implantable ultrasound device is safely tolerated in patients with recurrent glioblastoma immediately before systemic delivery of carboplatin-based chemotherapy. STUDY HYPOTHESIS: The blood-brain barrier can be safely opened using pulsed ultrasound prior to chemotherapy administration in patients with recurrent glioblastoma. Transient opening of the blood-brain barrier by pulsed ultrasound will increase the glioblastoma exposure to carboplatin-based chemotherapy and increase progression-free and overall survival in patients with recurrent glioblastoma.

Conditions

Glioblastoma; Glioma; Brain Tumor

Keywords

Blood brain barrier (BBB); Disruption; Low intensity pulsed ultrasound (LIPU); Sonocloud device; Glioblastoma (GBM); Brain Cancer; Carboplatin; Therapeutic Ultrasound

Outcome Measures

Primary Outcomes (1)

• Safety of transient disruption of the blood-brain barrier using the SonoCloud system in patients with recurrent glioblastoma.

  12 months

Secondary Outcomes (4)

• Maximum tolerated dose of ultrasound with the SonoCloud system for transient disruption of the BBB.

  12 months

• Quantification of the disruption of the BBB by the SonoCloud system using dynamic T1 contrast-enhanced MRI.

  12 months

• Progression-free survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.

  12 months

• Overall survival in patients treated with the SonoCloud system in combination with carboplatin chemotherapy.

  12 months

Study Arms (1)

SonoCloud + carboplatin

EXPERIMENTAL

SonoCloud : dose escalation Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

Device: SonoCloud; Drug: Carboplatin

Interventions

SonoCloud DEVICE

SonoCloud : dose escalation

SonoCloud + carboplatin

Carboplatin DRUG

Carboplatin : min 6 cycles - individual dose determination according to renal function and AUC

SonoCloud + carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 18 years.
• Subjects with recurrent glioma who have failed standard therapy with surgery and/or treatment with radiation and temozolomide.
• Patient eligible for Carboplatin-based chemotherapy
• Contrast-enhanced tumor less than 35 mm in diameter
• No risk of cerebral herniation
• Able to tolerate pre/post procedure steroid treatment
• Social security affiliated (in France)
• Able and willing to give signed and informed consent
• Normal biological status
• Hemoglobin ≥ 10 g/dl
• Platelets ≥ 100000/mm3
• Neutrophils ≥ 1500/mm3
• Normal creatine clearance ≥ 60ml/mn
• ASAT \< 3 N
• ALAT \< 3 N

You may not qualify if:

• Allergic to Iodine, Gadolinium, Xylocain
• Contra-indications to echographic contrast agent (microbubbles)
• Severe Renal insufficiency
• Hepatic insufficiency
• Possible toxic treatment for CNS
• Previously infected surgical field
• Uncontrolled epilepsy
• MRI contra-indications
• Hemostasis troubles thrombopenia \<75.000, TP \<60%, INR \>1.5, anti-platelet or anticoagulant therapy on-going)
• Active phlebitis or active pulmonary embolism
• Pregnant or currently breast-feeding
• Patients under judicial protection

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Groupe Hospitalier Pitié Salpetriere - Neurosurgery Department

Paris, 75013, France

Location

Related Publications (2)

• Asquier N, Bouchoux G, Canney M, Martin C, Law-Ye B, Leclercq D, Chapelon JY, Lafon C, Idbaih A, Carpentier A. Blood-brain barrier disruption in humans using an implantable ultrasound device: quantification with MR images and correlation with local acoustic pressure. J Neurosurg. 2019 Feb 1;132(3):875-883. doi: 10.3171/2018.9.JNS182001. Print 2020 Mar 1.

  PMID: 30717050 DERIVED

• Goldwirt L, Canney M, Horodyckid C, Poupon J, Mourah S, Vignot A, Chapelon JY, Carpentier A. Enhanced brain distribution of carboplatin in a primate model after blood-brain barrier disruption using an implantable ultrasound device. Cancer Chemother Pharmacol. 2016 Jan;77(1):211-6. doi: 10.1007/s00280-015-2930-5. Epub 2015 Dec 8.

  PMID: 26645405 DERIVED

MeSH Terms

Conditions

Glioblastoma; Glioma; Brain Neoplasms

Interventions

Carboplatin

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Ahmed Idbaih, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 1, 2014
• Study Start: July 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: October 12, 2018

Record last verified: 2018-10

Locations

FR (1)