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Multiple doser af neural stamcelle viroterapi (NSC-CRAd-S-pk7) til behandling af tilbagevendende højgradige gliomer

2. november 2026 opdateret af: City of Hope Medical Center

Et fase I-studie af multiple doser af neural stamcelle-baseret onkolytisk viroterapi (NSC-CRAd-S-pk7) administreret intracerebralt til patienter med tilbagevendende højgradige gliomer

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.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

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.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

36

Fase

  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • California
      • Duarte, California, Forenede Stater, 91010
        • Rekruttering
        • City of Hope Medical Center
        • Kontakt:
        • Ledende efterforsker:
          • Jana L. Portnow, MD
      • Stanford, California, Forenede Stater, 94305
    • Illinois
      • Chicago, Illinois, Forenede Stater, 60611
        • Suspenderet
        • Northwestern University
    • North Carolina
      • Winston-Salem, North Carolina, Forenede Stater, 27109
        • Ikke rekrutterer endnu
        • Wake Forest University
        • Kontakt:

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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
Procedure: Resection

Undergo surgical resection

Andre navne:
  • Intracerebral administration af NSC-crad-S-PK7 via intracavitært kateter
  • Fjernelse af CSF -prøver via et kateter placeret i den laterale cerebrale ventrikel
Biologisk: Neural Stem Cells-expressing CRAd-S-pk7

Given intracerebrally

Andre navne:
  • CRAd-S-pk7 indlæste NSC'er
  • NSC-CRAd-S-pk7
  • NSC-CRAd-S-pk7 Viroterapeutisk
  • NSC'er indlæst med CRAd-S-pk7
  • SC-CRAd-Survivin-pk7

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence of adverse events
Tidsramme: 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)
Tidsramme: 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]

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Neurale stamceller, der udtrykker CRAd-S-pk7 (NSC-CRAd-S-pk7) immunogenicitet
Tidsramme: Op til 30 dage efter fjernelse af Rickhams
Op til 30 dage efter fjernelse af Rickhams
Evalueret anvendelse af multiplex-immunoassays i cerebrospinalvæske (CSF) -prøver og RNA-sekventering i CSF, perifert blod og tumorvævsprøver.
Tidsramme: Op til 30 dage efter fjernelse af Rickhams
Op til 30 dage efter fjernelse af Rickhams
NSC-CRAd-S-pk7 migration within the brain
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: Baseline up to 2 years

Develop a biomathematical model for predicting tumor response to study treatment.
Baseline up to 2 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

City of Hope Medical Center

Samarbejdspartnere

National Cancer Institute (NCI)

Efterforskere

  • Ledende efterforsker: Jana L Portnow, MD, City of Hope Medical Center

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. maj 2023

Primær færdiggørelse (Anslået)

7. februar 2028

Studieafslutning (Anslået)

7. februar 2028

Datoer for studieregistrering

Først indsendt

22. november 2021

Først indsendt, der opfyldte QC-kriterier

22. november 2021

Først opslået (Faktiske)

1. december 2021

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

4. november 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

2. november 2026

Sidst verificeret

1. november 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 22338
  • P30CA033572 (U.S. NIH-bevilling/kontrakt)
  • 22338 (Anden identifikator: City of Hope Medical Center)
  • NCI-2022-10170 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

produkt fremstillet i og eksporteret fra U.S.A.

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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