Múltiples dosis de viroterapia con células madre neurales (NSC-CRAd-S-pk7) para el tratamiento de gliomas recurrentes de alto grado
Un estudio de fase I de dosis múltiples de viroterapia oncolítica basada en células madre neurales (NSC-CRAd-S-pk7) administradas por vía intracerebral a pacientes con gliomas recurrentes de alto grado
This phase I trial studies the safety of giving multiple intracerebral doses of NSC-CRAd-S-pk7 to treat patients with glioblastoma at first recurrence. NSC-CRAd-S-pk7 consists of neural stem cells that can target glioblastoma cells and carry a virus, which can kill cancer cells. Giving multiple doses of NSC-CRAd-S-pk7 may kill more tumor cells.
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
PRIMARY OBJECTIVE:
I. Determine the recommended maximum tolerated number of cycles (MTC) of intracavitary (ICT) administered neural stem cell-expressing CRAd-S-pk7 (NSCCRAd-S-pk7) for phase II testing based on dose-limiting toxicities (DLTs), the overall toxicity profile, and activity in patients with recurrent high-grade glioma (HGG).
II. Describe and compare the weekly dosing schedule (Treatment Schedule 4) to an every 2 week dosing schedule (Treatment Schedule 4a) of intracerebrally administered NSC-CRAd-S-pk7 based on DLTs, the overall toxicity profile, and activity in patients with glioblastoma at first recurrence.
III. Determine the recommended phase 2 dose schedule based on the overall toxicity profile, and activity in patients with recurrent high grade gliomas
SECONDARY OBJECTIVES:
I. I. Assess for evidence of biologic activity (cytotoxicity and anti-tumor immune responses) in posttreatment tissue samples.
II. Assess for the presence of NSC and/or CRAd-S-pk7 in post-treatment tissue samples.
III. Assess for possible development of antibody and T cell responses to the NSCs and/or CRAd-S-pk7 in CSF and blood.
IV. Assess for evidence of possible migration of NSCs and/or CRAd-S-pk7 outside of the brain and if so, determine if viral shedding is occurring.
V. Determine the persistence and intracerebral distribution of the NSCs and/or CRAd-S-pk7 whenever permission is given to perform a brain autopsy on a study participant.
VI. Estimate the rates of disease response, progression-free survival at 6 months (PFS6mo) and overall survival at 9 months (OS9mo) for all study participants and separately for the cohorts of glioblastoma patients at first recurrence treated at the MTC administered once a week or every 2 weeks.
VII. Identify a molecular signature of vulnerability for predicting which glioma patients will benefit most from treatment with NSC-CRAd-S-pk7.
VIII. Describe and compare changes in immunosuppressive and immunostimulatory cytokines in CSF from study participants enrolled to Treatment Schedules 4 and 4a.
IX. Assess for the presence of exhausted T cell phenotypes in CSF samples and compare the degree of T cell exhaustion in study participants enrolled to Treatment Schedules 4 and 4a.
OUTLINE:
Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks via a catheter placed during surgery. A second catheter is placed in the cerebral ventricle to obtain serial samples of CSF for correlative studies. Two weeks after the last dose of study agent is administered, study participants undergo a second surgical procedure to remove the catheters and obtain post-treatment tissue samples for analysis.
FINANCIAL ASSISTANCE:
There is funding to help with the cost of transportation, lodging, and meals for participants who qualify for financial assistance.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
California
-
Duarte, California, Estados Unidos, 91010
- Reclutamiento
- City of Hope Medical Center
-
Contacto:
- Jana L. Portnow
- Número de teléfono: 626-218-9393
- Correo electrónico: braintumortrials@coh.org
-
Investigador principal:
- Jana L. Portnow, MD
-
Stanford, California, Estados Unidos, 94305
- Reclutamiento
- Standford University
-
Contacto:
- Melanie H Hayden Gephart, MD
- Número de teléfono: 650-497-7777
- Correo electrónico: braintumorcenter@stanfordhealthcare.org
-
-
Illinois
-
Chicago, Illinois, Estados Unidos, 60611
- Suspendido
- Northwestern University
-
-
North Carolina
-
Winston-Salem, North Carolina, Estados Unidos, 27109
- Aún no reclutando
- Wake Forest University
-
Contacto:
- Glenn Lesser, MD
- Número de teléfono: 336-716-9527
- Correo electrónico: glesser@wakehealth.edu
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
-
Patient must be age >= 18 years
-
Patient has a Karnofsky performance status of >= 70%
-
Patient has a life expectancy of >= 3 months
- When determining the maximum tolerated number of treatment cycles (MTC): patient has a histologically confirmed diagnosis of a grade 3 or 4 glioma (eg., glioblastoma, grade 4 astrocytoma, grade 3 astrocytoma, grade 3 oligodendroglioma). (This part of the study has been completed).
- When enrolling to Treatment Schedules 4 and 4a: patient has glioblastoma at first recurrence.
-
Imaging studies show evidence of recurrent, supratentorial tumor(s).
-
Patient's high-grade glioma has recurred or progressed after prior treatment with brain radiation and temozolomide
-
The patient must be in need of surgery for tumor resection
-
Based on the neurosurgeon's judgment, there is no anticipated physical connection between the post-resection tumor cavity and the cerebral ventricles
-
Absolute neutrophil count (ANC) of >= 1000 cells/mm^3
-
Platelet count >= 100,000 cells/mm^3
-
Total bilirubin =< 2.0 mg/dl
-
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 4 times the institutional upper limit of normal
-
Serum creatinine =< the institutional upper limit of normal
-
At least 2 weeks from taking the last dose of a targeted agent
-
At least 4 weeks from the last dose of bevacizumab For temozolomide, an interval of 23 days is required from the last dose administered if the patient was recently treated with adjuvant temozolomide, consisting of temozolomide daily for 5 days, repeated every 28 days.
-
At least 2 weeks from taking the last dose of a targeted agent.
-
At least 4 weeks from the last dose of bevacizumab.
-
All significant toxicities from previous anticancer therapy must have stabilized to a new baseline or resolved.
-
All participants must have the ability to understand and the willingness to sign a written informed consent.
-
The effects of this treatment on a developing fetus are unknown. Therefore, female patients of childbearing potential and sexually-active male patients or who are able to impregnate their partner, must agree to use an effective method of contraception while participating in this study. Patients of childbearing potential must have a negative pregnancy test =< 2 week prior to registration.
Exclusion Criteria:
- Patient has multi-focal disease.
- Patient is receiving radiation, chemotherapy, or another investigational agent.
- Patient has had prior therapy with neural stem cells.
- Patient has not recovered from any toxicity (> grade 1) of prior therapies, except alopecia.
- Patient is unable to undergo a brain MRI.
- Patient has chronic or active viral infections of the central nervous system (CNS).
- Patient has a coagulopathy or bleeding disorder.
- Patient has an uncontrolled illness including ongoing or active infection.
- Patient has another active malignancy.
- Patient is pregnant or breastfeeding.
- A patient has a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the safety monitoring requirements and completion of treatment according to this protocol.
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: Treatment (NSC-CRAd-S-pk7)
Patients undergo standard surgical resection, and during surgery the first dose of study agent is injected into the wall of the resection cavity. Patients then receive three additional doses every week or every two weeks (depending on when they enroll in the study) via a catheter that was placed during surgery |
Undergo surgical resection
Otros nombres:
Given intracerebrally
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidence of adverse events
Periodo de tiempo: Up to 30 days post removal of Rickhams
|
Assessed using the Common Terminology Criteria for Adverse Events version 5.0. |
Up to 30 days post removal of Rickhams
|
|
Progression-free survival (PFS)
Periodo de tiempo: From the time of surgery to the event date of progression, assessed at 6 months]
|
Will estimate the rate 90% confidence interval (CI) for PFS at 6 months and use Kaplan Meier methods to estimate median PFS for all study participants as well as for the cohorts of glioblastoma (GBM) participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 given once a week or every two weeks. |
From the time of surgery to the event date of progression, assessed at 6 months]
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Células madre neurales que expresan inmunogenicidad de CRAd-S-pk7 (NSC-CRAd-S-pk7)
Periodo de tiempo: Hasta 30 días después de la eliminación de Rickhams
|
Hasta 30 días después de la eliminación de Rickhams
|
|
|
Evaluado usando inmunoensayos multiplex en muestras de líquido cefalorraquídeo (CSF) y secuenciación de ARN en MUESTRAS DE CSF, sangre periférica y tejido tumoral.
Periodo de tiempo: Hasta 30 días después de la eliminación de Rickhams
|
Hasta 30 días después de la eliminación de Rickhams
|
|
|
NSC-CRAd-S-pk7 migration within the brain
Periodo de tiempo: Up to 30 days post removal of Rickhams
|
Neural stem-cells and/or free viral particles will be assessed in samples of post-treatment tissue samples. |
Up to 30 days post removal of Rickhams
|
|
NSC-CRAd-S-pk7 migration outside the brain
Periodo de tiempo: Up to 30 days post removal of Rickhams
|
4. Neural stem-cells and/or free viral particles will be assessed in samples of CSF, peripheral blood, urine, oral and rectal mucosa (via swabbing), and skin at the injection site (also via swabbing). |
Up to 30 days post removal of Rickhams
|
|
Disease response
Periodo de tiempo: Up to 2 years
|
Response Assessment in Neuro-Oncology Criteria will be used to assess response on brain magnetic resonance imaging in all study participants who receive at least 80% of the planned doses of study treatment. Disease response will be similarly assessed for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAD-S-pk7 once a week or every two weeks. |
Up to 2 years
|
|
Overall survival (OS)
Periodo de tiempo: From time of surgery to date of death, assessed at 9 months
|
Will estimate the rate 90% CI for OS at 9 months and use Kaplan Meier methods to estimate median OS for all study participants as well as for the cohorts of GBM participants at first recurrence who will be treated with 4 doses of NSC-CRAd-S-pk7 once a week or every two weeks. |
From time of surgery to date of death, assessed at 9 months
|
|
Changes in HSPG and survivin expression
Periodo de tiempo: Baseline up to 2 years
|
Changes in survivin expression by immunohistochemistry IHC in pre- and post-treatment tissue to see if there is a relationship with disease response. |
Baseline up to 2 years
|
|
Changes in immune cell populations
Periodo de tiempo: Baseline up to 2 years
|
Changes in immune cell populations in the tumor microenvironment in pre- and post-treatment tumor tissue samples will be assessed by Vectra Spectral Imaging. |
Baseline up to 2 years
|
|
Changes in tumor growth
Periodo de tiempo: Baseline up to 2 years
|
Develop a biomathematical model for predicting tumor response to study treatment. |
Baseline up to 2 years
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Jana L Portnow, MD, City of Hope Medical Center
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
- 22338
- P30CA033572 (Subvención/contrato del NIH de EE. UU.)
- 22338 (Otro identificador: City of Hope Medical Center)
- NCI-2022-10170 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
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.
producto fabricado y exportado desde los EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .