Multisite open-label randomized phase II clinical trial in newly diagnosed glioblastoma treated by concurrent TemoRadiation and adjuvant temozolomide +/- ultrasound-induced blood brain barrier opening - SonoFIRST

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical,Diagnostic,Therapeutic Techniques and Equipment [E]-Surgical Procedures, Operative [E04], Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2024-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

H2020-EIT Health European Union

External identifiers

EU CT number

2024-511880-27-00

EudraCT number

2020-001488-10

ClinicalTrials.gov

NCT04614493

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

clinical efficacy based on comparison of median PFS (Progression Free Survival) assessed by local investigator between the standard of care treatment with ultrasound BBB opening versus standard of care treatment alone.

Secondary objectives 4

1. Survival improvement
2. Patient quality of life preservation
3. Patient intellectual preservation
4. Safety confirmation of SonoCloud-9 induced efficient grade 3 BBB opening

Conditions and MedDRA coding

Newly diagnosed Glioblastoma (IDH wild-type) patients at initial radiological diagnosis eligible for tumor resection, and for the standard of care including concurrent temoradiation followed by adjuvant TMZ with or without Tumor Treating Fields*. (*Tumor Treating Fields is applicable only in participating centers in France)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Brain MRI with suspicion of newly diagnosed IDH wild type GBM
2. Supratentorial tumor
3. T1W Tumor enhancement of ≤ 7cm
4. Eligible for partial or complete surgical resection and for concurrent TemoRadiation followed by adjuvant TMZ (according to Stupp protocol) with or without Tumor Treating Fields* - (*Tumor Treating Fields is applicable only in participating centers in France)
5. Patient ≥ 18 years, able and willing to give signed and informed consent. Inclusion for patients aged >70 years should be validated in neuro-oncology tumor board (RCP)
6. KPS ≥70

Exclusion criteria 16

1. Contra indication for sonication
2. a. Patients with multifocal tumor (unless all localized in a 70 mm diameter area accessible to ultrasound field) or located in posterior fossa tumor
3. b. Patient with diffuse FLAIR abnormalities attributable to Gliomatosis
4. c. Patients with evidence of uncontrolled intracranial pressure
5. d. Patients with uncontrolled epilepsy
6. e. Patients with medical need to continue antiplatelet or antithrombotic treatment
7. f. Pregnant or breastfeeding women (blood pregnancy test)
8. g. Patients with contra-indications to MRI or known sensitivity/allergy to gadolinium, or other intravascular contrast agents
9. h. Known history of hypersensitivity reactions to perflutren lipid microsphere components or to any of the inactive ingredients in Luminity®/Definity®
10. i. Patients with known intracranial aneurism, with and/or unremovable coils, clips, shunts, intravascular stents, wafer, non resorbable dura substitute, or reservoirs
11. j. Patients with an uncontrolled intercurrent illness or any pre-existing comorbidities that in the Investigator’s opinion may prevent the implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud or may be cofounding for evaluation of the clinical trial
12. k. Patients with the following are not eligible: • Known arterial hypertension grade 3 or higher without adequate control on medications • Known or suspected unstable active or chronic infections requiring systemic treatment • Known significant cardiac disease: right-to-left shunts, Unstable angina pectoris, Symptomatic congestive heart failure, Unstable cardiac arrhythmia • Known significant pulmonary disease: severe pulmonary hypertension (pulmonary artery pressure > 90 mmHg), uncontrolled systemic hypertension, adult respiratory distress syndrome, or Pneumonitis • Known Severe renal failure • Known serious myelosuppression • Known Psychiatric illness/social situations that would limit compliance with study requirements • Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient’s safety or study endpoints • Known immunodeficiency disease or treatments (HIV) • Known viral or bacterial chronic/acute disease (potential blood borne infections that could result in meningitis or brain abscess) • Coeliac disease or wheat allergy • Known liver dysfunction
13. l. Patients under judicial protection
14. m. Patients with any following prohibited treatments: • Any investigational medicinal product within 30 days prior to inclusion and during the study • Antibiotics with known neurotoxicity (eg, aminoglycosides, cephalosporin, quinolones), unless substitution is not possible, • Non-absorbable material (dura matter substitute, hemostatic agent…) • Any other drug according investigator to cause cerebral toxicity due to BBB opening • Contra-indications to temozolomide
15. n. Implantation of the SC-9 not possible according to neurosurgeon (Any patient morphological characteristics (e.g. skin thickness >9mm), which, from neurosurgeons’ opinion, prevent implantation of the device or may impair the ability of the patient to receive treatment with SonoCloud, would be excluded)
16. Contra indication Optune: If TTF treatment is initiated (only available in France), the investigator must first ensure that the patient has no contraindications to the Optune device (See page 41)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS is defined as the time between randomization and disease progression which is the first documented tumor progression (per local Investigator assessment according to the RANO criteria) or death due to any cause.

Secondary endpoints 10

1. crPFS: central review Progression Free Survival according to RANO criteria assessed by central independent review
2. iPFS: immune Progression Free Survival according to iRANO criteria assessed by local investigator
3. OS: Overall Survival
4. KPS: Karnofsky Performance Status assessed at all visits until progression.
5. MMSE: Mini Mental Status Examination mean score assessed at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression.
6. QLQ-C30: the C30 Quality of Life Questionnaire (QLQ) will be assessed at using the European Organization for Research and Treatment of Cancer, at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression.
7. QLQ-BN20PROM: the BN20 Quality of Life Questionnaire (QLQ) will be assessed at using the European Organization for Research and Treatment of Cancer, at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression.
8. PainPROM: pain score from surgical area at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression. This will be assessed using visual analogic scale.
9. EstheticalPROM: score in self-confidence concerning esthetical dimension of surgical scar at randomization, pre-TemoRadiation visit, C1 (baseline after surgery/radiotherapy), C3, C6, M11 and M18 until progression using esthetical comfort question equivalent to q39 of QLQ-BR23 questionnaire.
10. Safety confirmation is assessed by the frequency and severity of AE (incidence of AE summarized by system organ class and/or preferred term and severity) based on the Common Terminology Criteria for Adverse Events, version 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Prof. Ahmed IDBAIH

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Prof. Ahmed IDBAIH

Locations

2 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications