SC9-GBM-01: Safety and Efficacy of Transient Opening of the Blood-brain Barrier (BBB) With the SonoCloud-9

Sponsor

CarThera (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03744026

Collaborator

(none)

Enrollment

Locations

Arm

46.4

Anticipated Duration (Months)

5.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Recurrent glioblastoma (GBM) is a disease with high unmet clinical need. The standard of care for patients with GBM includes surgery, radiotherapy and chemotherapy. Despite this aggressive treatment, the overall median survival of patients with GBM remains at 15-20 months.

In more than 95% of cases, tumor recurrence is observed within 2 cm to 3 cm of the resection cavity within 4-7 months after initial treatments. One of the main causes of recurrence is the inability of chemotherapies to enter the brain from the systemic circulation due to the blood-brain barrier (BBB). The BBB is unique to cerebral blood vessels and blocks most drugs from entering the brain in sufficient concentrations.

The SonoCloud-9 (SC9) System delivers ultrasound to locally and transiently increase the permeability of the BBB to allow the passage of drugs into the cerebral parenchyma. The SC9 is dimensioned to cover the resection area and surrounding tissues in patients with recurrent GBM. The large sonicated volume covered by the SC9 device allows for broad BBB disruption and should allow for carboplatin chemotherapy to penetrate the surrounding tumor infiltrative area. By enhancing drug concentrations, it is hypothesized that further disease progression will be prevented.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma, Adult	Device: SonoCloud-9 Drug: Carboplatin	Phase 1/Phase 2

Detailed Description

This will be an open-label, Phase 1/2a, multicenter, single-arm, interventional trial that will first evaluate the dose limiting toxicity (DLT) of escalating numbers of ultrasound beams at constant acoustic pressure using a standard escalation (Phase 1) and then confirm the safety and efficacy of BBB opening (Phase 2a expansion).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Study to Evaluate the Safety and the Efficacy of Transient Opening of the Blood-brain Barrier (BBB) by Low Intensity Pulsed Ultrasound With the SonoCloud-9 Implantable Device in Recurrent Glioblastoma Patients Eligible for Surgery and for Carboplatin Chemotherapy

Actual Study Start Date :

Feb 18, 2019

Actual Primary Completion Date :

Jun 23, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SonoCloud-9 Ultrasound + Carboplatin SonoCloud-9 Carboplatin: 6 cycles (every 4 weeks)	Device: SonoCloud-9 Escalating numbers of ultrasound beams at constant acoustic pressure Drug: Carboplatin Dose of carboplatin infusion is AUC4-6

Arm

Intervention/Treatment

Experimental: SonoCloud-9 Ultrasound + Carboplatin

SonoCloud-9 Carboplatin: 6 cycles (every 4 weeks)

Device: SonoCloud-9

Escalating numbers of ultrasound beams at constant acoustic pressure

Drug: Carboplatin

Dose of carboplatin infusion is AUC4-6

Outcome Measures

Primary Outcome Measures

Dose limiting toxicity (DLT) of number of activated ultrasound beams [15 days after the first sonication treatment]
DLT will be evaluated using imaging (MRI) and clinical examination, as CTCAE that occurs within 2 weeks of the first sonication and that does not respond to optimal medical management (including steroids) within 7 days.
Blood-Brain Barrier (BBB) opening [At the end of the first three sonication treatments (treatment occurs every 4 weeks)]
BBB opening will be evaluated by contrast-enhanced T1w magnetic resonance imaging (MRI)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Age ≥ 18 years, able and willing to give signed and informed consent.
Patient with histologically proven recurrent de novo GBM:
After at least a first-line standard of care (maximal safe resection, if feasible, radiation with temozolomide [TMZ], then TMZ);
Any recurrence;
Bevacizumab-naïve.*
Patient eligible for carboplatin-based chemotherapy.
Patient eligible for a surgical resection.
Maximal tumor diameter at inclusion (pre surgery) ≤ 70 mm in T1wMRI.
Patients should be stable, without evidence of a midline shift, significant peritumoral edema, or rapid progression of clinical symptoms.
Karnofsky performance status ≥ 70.
Patient receiving prednisone dose ≤ 40 mg (dexamethasone ≤ 6 mg) for at least 7 days.

Key Exclusion Criteria:

Multifocal tumor (unless all localized in a 70 mm diameter area).
Patients at risk of surgery site infection (2 or more previous craniotomies, neurosurgery within the last 3 months, poor skin condition, and/or previously infected surgical field).
Posterior fossa tumor.
Uncontrolled epilepsy.
Patients with evidence of uncontrolled intracranial pressure.
Patients with known intracranial aneurism or having presented intra-tumor spontaneous hemorrhage.
Patients with coils, clips, shunts, intravascular stents, and/or unremovable wafer, non resorbable dura substitute, or reservoirs.
Patients with medical need to continue antiplatelet therapy.
Patients with known or suspected active or chronic infections.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611
2	MD Anderson Cancer Center	Houston	Texas	United States	77030
3	CHU	Angers		France
4	Hôpital Neurologique Pierre Wertheimer	Bron		France
5	Hôpital de La Timone	Marseille		France
6	Hôpital de la Pitié-Salpêtrière	Paris		France