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Silmitasertib (CX-4945) i kombination med kemoterapi for recidiverende refraktære solide tumorer

5. oktober 2026 opdateret af: Giselle Sholler, Milton S. Hershey Medical Center

Fase I/II undersøgelse af Silmitasertib (CX-4945) i kombination med kemoterapi hos børn og unge voksne med recidiverende refraktære solide tumorer

The purpose of this study is to evaluate the investigational drug, silmitasertib (a pill taken by mouth), in combination with FDA approved drugs for solid tumors. An investigational drug is one that has not been approved by the U.S. Food & Drug Administration (FDA), or any other regulatory authorities around the world for use alone or in combination with any drug, for the condition or illness it is being used to treat.

The goals of this part of the study are:

  • Establish a recommended dose of silmitasertib in combination with chemotherapy
  • Test the safety and tolerability of silmitasertib in combination with chemotherapy in subjects with cancer
  • To determine the activity of study treatments chosen based on:
  • How each subject responds to the study treatment
  • How long a subject lives without their disease returning/progressing

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

104

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

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

Studiekontakt

Studiesteder

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, QC H3S 2G4
  • Forenede Stater
    • Alabama
      • Birmingham, Alabama, Forenede Stater, 35233
        • Rekruttering
        • University of Alabama/Children's of Alabama
        • Kontakt:
        • Ledende efterforsker:
          • Elizabeth Alva
    • Arizona
      • Phoenix, Arizona, Forenede Stater, 85016
        • Rekruttering
        • Phoenix Children's Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Francis Eshun
    • California
      • Oakland, California, Forenede Stater, 94609
        • Rekruttering
        • UCSF Benioff Children's Hospital Oakland
        • Ledende efterforsker:
          • Jennifer Michlitsch
        • Kontakt:
      • Sacramento, California, Forenede Stater, 95817
        • Rekruttering
        • UC Davis Comprehensive Cancer Center
        • Kontakt:
        • Ledende efterforsker:
          • Marcio Malogolowkin
      • San Diego, California, Forenede Stater, 92123
        • Rekruttering
        • Rady Children's Hospital
        • Kontakt:
        • Ledende efterforsker:
          • William Roberts
    • Connecticut
      • Hartford, Connecticut, Forenede Stater, 06106
    • Florida
      • Gainesville, Florida, Forenede Stater, 32611
        • Rekruttering
        • University of Florida
        • Ledende efterforsker:
          • Joanne Lagmay
        • Kontakt:
      • Miami, Florida, Forenede Stater, 33155
      • Orlando, Florida, Forenede Stater, 32806
      • St. Petersburg, Florida, Forenede Stater, 33701
        • Rekruttering
        • All Children's Hospital Johns Hopkins Medicine
        • Kontakt:
        • Ledende efterforsker:
          • Jennifer Dean
      • Tampa, Florida, Forenede Stater, 33614
        • Rekruttering
        • St. Joseph's Children's Hospital
        • Ledende efterforsker:
          • Don Eslin
        • Kontakt:
    • Hawaii
      • Honolulu, Hawaii, Forenede Stater, 96813
        • Rekruttering
        • Kapiolani Medical Center for Women and Children
        • Kontakt:
        • Ledende efterforsker:
          • Kelley Hutchins
    • Kentucky
      • Louisville, Kentucky, Forenede Stater, 40202
        • Rekruttering
        • Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
        • Ledende efterforsker:
          • Michael Ferguson
        • Kontakt:
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Rekruttering
        • Children's Hospital of Michigan/Wayne State University
        • Kontakt:
        • Ledende efterforsker:
          • Alissa Martin
    • Missouri
      • Kansas City, Missouri, Forenede Stater, 64108
        • Rekruttering
        • Children's Mercy Hospitals and Clinics
        • Ledende efterforsker:
          • Kevin Ginn
        • Kontakt:
      • St Louis, Missouri, Forenede Stater, 63104
        • Rekruttering
        • Cardinal Glennon Children's Medical Center
        • Ledende efterforsker:
          • William Ferguson
        • Kontakt:
    • New Jersey
      • Hackensack, New Jersey, Forenede Stater, 07601
        • Rekruttering
        • Hackensack University Medical Center
        • Ledende efterforsker:
          • Katharine Offer
        • Kontakt:
    • Pennsylvania
      • Hershey, Pennsylvania, Forenede Stater, 17033
        • Rekruttering
        • Penn State Milton S. Hershey Medical Center and Children's Hospital
        • Kontakt:
        • Ledende efterforsker:
          • Valerie Brown
    • Rhode Island
      • Providence, Rhode Island, Forenede Stater, 02903
        • Rekruttering
        • Hasbro Children's Hospital
        • Ledende efterforsker:
          • Bradley DeNardo
        • Kontakt:
    • Tennessee
      • Nashville, Tennessee, Forenede Stater, 37232
        • Rekruttering
        • Monroe Carrell Jr. Children's Hospital at Vanderbilt
        • Kontakt:
        • Ledende efterforsker:
          • Daniel Benedetti
    • Texas
      • Dallas, Texas, Forenede Stater, 75235
        • Rekruttering
        • Children's Medical Center
        • Ledende efterforsker:
          • Tanya Watt
        • Kontakt:
    • Utah
      • Salt Lake City, Utah, Forenede Stater, 84113
        • Rekruttering
        • Primary Children's Hospital
        • Ledende efterforsker:
          • Matthew Dietz
        • Kontakt:
    • Virginia
      • Richmond, Virginia, Forenede Stater, 23284
        • Rekruttering
        • Virginia Commonwealth University
        • Kontakt:
        • Ledende efterforsker:
          • Madhu Gowda

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

Ikke ældre end 30 år (Barn, Voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  1. Age: Less than 30 years old at initial diagnosis

  2. Pathology All subjects must have a confirmed diagnosis of tumor type. Phase I: Relapsed/refractory solid tumors: Neuroblastoma, Ewing Sarcoma, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma

    Phase II:

    • Relapsed/refractory Neuroblastoma
    • Relapsed/refractory Ewing sarcoma

  3. Tumor assessment:

    Disease assessment is required for eligibility and must be done after last dose of previous therapy and prior to first dose of study drug.

  4. Disease Status:

    Relapsed/Refractory Neuroblastoma Relapsed disease defined as neuroblastoma that was previously in remission after standard therapy (at least 4 cycles of aggressive multi-drug induction chemotherapy, with or without radiation and surgery, followed by immunotherapy, or according to a standard high-risk treatment/neuroblastoma protocol) and has now relapsed and is in any number of relapses.

    Refractory disease defined as High-risk neuroblastoma (as defined by INRG) that failed to achieve CR after at least 4 cycles of aggressive multi-drug induction chemotherapy, progression during upfront therapy or with disease remaining after standard immunotherapy.

    International Neuroblastoma Risk Group Staging System (INRG) High Risk NB defined as one of the following:

    1. Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification
    2. Age ≥ 547 days and INRG Stage M regardless of biologic features
    3. Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to Stage M without systemic chemotherapy
    4. Age ≥ 547 days of age initially diagnosed with INRG Stage L1, L2, or MS who have progressed to Stage M without systemic chemotherapy

    Relapsed/refractory Sarcoma Subjects that have relapsed following standard of care therapy or having progressed during standard of care therapy. Standard of care therapy for sarcoma includes multi-agent chemotherapy with local control consisting of either surgery or radiation therapy.

  5. Measurable or evaluable disease, including at least one of the following:

    • Measurable tumor by CT or MRI
    • MIBG or PET that is positive for disease
    • Bone Marrow biopsy/aspirate that is positive for disease

  6. Timing from prior therapy:

    Subjects must have fully recovered from the acute toxic effects of all prior anti- cancer therapy and be within the following timelines:

    1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study.

    2. Small Molecule Inhibitors (anti-neoplastic agent): At least 2 weeks from the completion of therapy with a small molecule inhibitor.

    3. Immunotherapy: At least 4 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines, CAR-T cells, anti-GD2 Monoclonal antibodies (ex. naxitamab, dinutuximab, etc.).

    4. Radiotherapy: At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.

    5. Stem Cell Transplant:

      • Allogeneic: No evidence of active graft vs. host disease
      • Allogeneic/Autologous: ≥ 2 months must have elapsed since transplant.

    6. MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.

  7. Subjects must have a Lansky or Karnofsky Performance Scale score of >/= 50.

  8. Subjects must have adequate organ function at the time of enrollment:

    • Cardiac: Subjects must have a QTcF ≤ 480 msc.
    • Hematological: Hematological recovery as defined by ANC ≥750/μL
    • Liver: Adequate liver function as defined by AST and ALT <5x upper limit of normal
    • Renal: Subjects must have adequate renal function defined as:
    • estimated Glomerular Filtration rate (eGFR) as calculated from the Bedside Schwartz equation (for subjects < 17 years old) (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Bedside Schwartz equation is: [(0.413) X (Height in cm)] / SCr
    • estimated Glomerular Filtration rate (eGFR) as calculated from the Cockcroft and Gault formula (for subjects ≥17 years old (in units of mL/min/1.73 m2) or via radioisotope GFR of ≥ 70 mL/min/1.73 m2. The Cockcroft and Gault formula is: [(140-age) x (Wt in kg) x (0.85 if female)] / (72 x SCr)
    • OR a 24 hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2

  9. Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.

  10. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).

Exclusion Criteria:

  1. Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.

  2. Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the hematological and bone marrow suppression effects of prior therapy.

  3. Subjects who are currently receiving Vitamin K antagonists (warfarin).

  4. Subjects who are currently receiving the class of lipid-lowering medications HMG-CoA reductase inhibitors (statins).

  5. Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.

  6. Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

  7. Subjects with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the subject's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results.

  8. Subjects with any of the following gastrointestinal disorders:

    1. Active malabsorption (e.g. short gut) syndrome.
    2. Uncontrolled diarrhea (excess of 4 stools/day)
    3. Gastritis, ulcerative colitis, Chron's disease or hemorrhagic coloproctitis
    4. History of gastric or small bowel surgery involving any extent of gastric or small bowel resection

  9. Lactating subjects are not eligible unless they have agreed to not breastfeed their infants. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing subject with silmitasertib. (NOTE: breast milk cannot be stored for future use while the nursing subject is being treated on study.)

  10. Subjects with a history of any other malignancy.

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: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Phase I- Dose level 1

Silmitasertib 600 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Medicin: Silmitasertib

Capsules

Andre navne:
  • CX-4945
Medicin: Irinotecan

IV

Medicin: Temozolomide

Oral or IV

Medicin: Vincristine

IV
Eksperimentel: Phase I- Dose level 2

Silmitasertib 800 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Medicin: Silmitasertib

Capsules

Andre navne:
  • CX-4945
Medicin: Irinotecan

IV

Medicin: Temozolomide

Oral or IV

Medicin: Vincristine

IV
Eksperimentel: Phase II- Relapsed/refractory Neuroblastoma

Silmitasertib RP2D twice a day plus Irinotecan and Temozolomide
Medicin: Silmitasertib

Capsules

Andre navne:
  • CX-4945
Medicin: Irinotecan

IV

Medicin: Temozolomide

Oral or IV
Eksperimentel: Phase II- Relapsed/refractory Ewing sarcoma

Silmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide
Medicin: Silmitasertib

Capsules

Andre navne:
  • CX-4945
Medicin: Irinotecan

IV

Medicin: Temozolomide

Oral or IV

Medicin: Vincristine

IV

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Tidsramme: 2 years plus 30 days

To characterize the safety profile of silmitasertib in combination with chemotherapy
2 years plus 30 days
Phase I- Number of Participants with Dose Limiting Toxicities to determine RP2D
Tidsramme: 21 days

To determine the Recommended Phase 2 Dose (RP2D) of silmitasertib in combination with chemotherapy
21 days
Phase II- Determine the Overall Response Rate (ORR) of Participants using INRC
Tidsramme: 2 years

To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts, based upon Overall response rate (ORR)
2 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
Tidsramme: 2 years

To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Overall response rate (ORR)
2 years
Number of participants with progression free survival (PFS) during study
Tidsramme: 2 years

To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Progression Free Survival (PFS)
2 years
Phase II- Length of time that participants experience Overall Survival (OS)
Tidsramme: 7 years

To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Overall Survival (OS)
7 years
Phase II- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Tidsramme: 2 years plus 30 days

To characterize the safety profile of silmitasertib in combination with chemotherapy
2 years plus 30 days
Phase II - Determine the Disease Control Rate (DCR) of participants based on response
Tidsramme: 2 years plus 30 days

Disease Control Rate (DCR): Defined as CR + PR + MR + SD for Neuroblastoma (INRC) and CR + PR + SD for Ewing Sarcoma (RECIST v1.1).
2 years plus 30 days

Samarbejdspartnere og efterforskere

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

Sponsor

Milton S. Hershey Medical Center

Efterforskere

  • Studiestol: Chandrika Behura, MD, Penn State Health Children's Hospital

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Hjælpsomme links

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)

30. oktober 2024

Primær færdiggørelse (Anslået)

1. november 2030

Studieafslutning (Anslået)

1. november 2035

Datoer for studieregistrering

Først indsendt

2. august 2024

Først indsendt, der opfyldte QC-kriterier

2. august 2024

Først opslået (Faktiske)

7. august 2024

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

6. oktober 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

5. oktober 2026

Sidst verificeret

1. oktober 2026

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • BCC021

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

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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