- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT05864534
[Prueba de dispositivo que no está aprobado o aprobado por la FDA de EE. UU.]
Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB.
The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Eligible patients will undergo implant of the Soncloud-9 device within 1-5 weeks of completion of radiotherapy. About 1-3 weeks after surgery, patients will undergo sonication and intravenous administration of balstilimab, botensilimab and liposomal doxorubicin. Brain MRI will be done to quantify extent of blood brain barrier opening. The dose for balstilimab is 450 mg every 3 weeks. The dose for botensilimab is 1mg/kg every 6 weeks. The dose for liposomal doxorubicin is 30 mg every 3 weeks. Sonication and administration of study agents will continue every 3 weeks (21 days= 1 cycle) for a total of 9 cycles (approx. 6 months). Additional cycles may be considered if deemed beneficial and in the patient's best interest. Blood samples for circulating tumor DNA will also be collected before and after each sonication. The first 6 patients will comprise a safety run-in cohort with intensified safety monitoring through the end of the second cycle.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Have newly diagnosed pathologically proven glioblastoma, isocitric dehydrogenase-1/2 wild-type
- Tumor with methyl guanine methyl transferase (MGMT) gene promoter unmethylated
- Available paraffin embedded tumor tissue for the study
- Have completed standard radiotherapy with or without temozolomide
- 18 years of age or older
- Able to undergo contrast-enhanced MRI
- Have an Eastern Cooperative Oncology Group/World Health Organization performance status ≤ 2
- Size and location of the residual tumor and/or resection cavity must allow to be able to be covered by the sonication field
- Have not received any prior treatment with immunotherapeutic agents treatments for glioblastoma or other indications
- Have the ability to understand and willingness to sign a written informed consent prior to registration on study.
- Be willing and able to comply with the protocol.
- Have adequate organ and bone marrow function
- Agree to use adequate contraception if appropriate
Exclusion Criteria: Patients will be ineligible if they have:
- Multifocal tumor (unless all localized in a 50-mm diameter area accessible to ultrasound field) or tumor located in the posterior fossa.
- Uncontrolled epilepsy.
- Received other investigational agents within 2 weeks of registration
- Received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.
- Contraindication to checkpoint inhibitor therapy (e.g., history of autoimmune disease)
- Uncontrolled illness
- History of active malignancy other than the brain tumor within 12 months prior to registration.
- Are pregnant or breastfeeding.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Blood-brain barrier opening with concomitant BAL, BOT, DOX
Patients will undergo implantation of Sonocloud-9 after completion of radiotherapy. Within 21 days after implant, ultrasound-based BBB opening with concomitant administration of DOX (30 mg) + BAL (450 mg) every 3 weeks, and BOT (dose 1mg/kg) every 6 weeks will be initiated. |
Balstilimab 450 mg IV over 30 minutes every 3 weeks
Otros nombres:
Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks
Otros nombres:
Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks
Otros nombres:
Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Unacceptable toxicity rate
Periodo de tiempo: 42 days
|
Unacceptable toxicity rate in cycle 1 of < 33% |
42 days
|
|
Landmark survival analyses
Periodo de tiempo: 18 months
|
Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival. |
18 months
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Predictive value of phospho-extracellular signal-related kinase (p-ERK) expression
Periodo de tiempo: 18 months
|
Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy |
18 months
|
|
Response rate
Periodo de tiempo: 18 months
|
Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor |
18 months
|
Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Patterns of recurrence
Periodo de tiempo: 18 months
|
Patterns of recurrence by magnetic resonance imaging related to sonication field |
18 months
|
|
Immune profile
Periodo de tiempo: 12 months
|
Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival |
12 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Adam Sonabend, MD, Northwestern University
- Director de estudio: Roger Stupp, MD, Northwestern University
Publicaciones y enlaces útiles
Publicaciones Generales
- Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015 Feb 1;194(3):950-9. doi: 10.4049/jimmunol.1401686. Epub 2014 Dec 24.
- O'Malley DM, Oaknin A, Monk BJ, Selle F, Rojas C, Gladieff L, Berton D, Leary A, Moore KN, Estevez-Diz MDP, Hardy-Bessard AC, Alexandre J, Opperman CP, de Azevedo CRAS, Randall LM, Feliu WO, Ancukiewicz M, Ray-Coquard I. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. Gynecol Oncol. 2021 Nov;163(2):274-280. doi: 10.1016/j.ygyno.2021.08.018. Epub 2021 Aug 25.
- Treat LH, McDannold N, Zhang Y, Vykhodtseva N, Hynynen K. Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol. 2012 Oct;38(10):1716-25. doi: 10.1016/j.ultrasmedbio.2012.04.015. Epub 2012 Jul 19.
- Beccaria K, Sabbagh A, de Groot J, Canney M, Carpentier A, Heimberger AB. Blood-brain barrier opening with low intensity pulsed ultrasound for immune modulation and immune therapeutic delivery to CNS tumors. J Neurooncol. 2021 Jan;151(1):65-73. doi: 10.1007/s11060-020-03425-8. Epub 2020 Feb 28.
- Duerinck J, Schwarze JK, Awada G, Tijtgat J, Vaeyens F, Bertels C, Geens W, Klein S, Seynaeve L, Cras L, D'Haene N, Michotte A, Caljon B, Salmon I, Bruneau M, Kockx M, Van Dooren S, Vanbinst AM, Everaert H, Forsyth R, Neyns B. Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. J Immunother Cancer. 2021 Jun;9(6):e002296. doi: 10.1136/jitc-2020-002296.
- Shimozaki K, Sukawa Y, Sato Y, Horie S, Chida A, Tsugaru K, Togasaki K, Kawasaki K, Hirata K, Hayashi H, Hamamoto Y, Kanai T. Analysis of risk factors for immune-related adverse events in various solid tumors using real-world data. Future Oncol. 2021 Jul;17(20):2593-2603. doi: 10.2217/fon-2020-0861. Epub 2021 Apr 21.
- Kim KS, Habashy K, Gould A, Zhao J, Najem H, Amidei C, Saganty R, Arrieta VA, Dmello C, Chen L, Zhang DY, Castro B, Billingham L, Levey D, Huber O, Marques M, Savitsky DA, Morin BM, Muzzio M, Canney M, Horbinski C, Zhang P, Miska J, Padney S, Zhang B, Rabadan R, Phillips JJ, Butowski N, Heimberger AB, Hu J, Stupp R, Chand D, Lee-Chang C, Sonabend AM. Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood-brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas. Neuro Oncol. 2024 Nov 4;26(11):2044-2060. doi: 10.1093/neuonc/noae135.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- NU23C03
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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