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Silmitasertib (CX-4945) in Kombination mit Chemotherapie bei rezidivierten refraktären soliden Tumoren

5. Oktober 2026 aktualisiert von: Giselle Sholler, Milton S. Hershey Medical Center

Phase-I/II-Studie zu Silmitasertib (CX-4945) in Kombination mit Chemotherapie bei Kindern und jungen Erwachsenen mit rezidivierten refraktären soliden Tumoren

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

Studienübersicht

Status

Rekrutierung

Bedingungen

Intervention / Behandlung

Studientyp

Interventionell

Einschreibung (Geschätzt)

104

Phase

  • Phase 2
  • Phase 1

Kontakte und Standorte

Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.

Studienkontakt

Studienorte

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

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

Nicht älter als 30 Jahre (Kind, Erwachsene)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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.

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Sequenzielle Zuweisung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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
Arzneimittel: Silmitasertib

Capsules

Andere Namen:
  • CX-4945
Arzneimittel: Irinotecan

IV

Arzneimittel: Temozolomide

Oral or IV

Arzneimittel: Vincristine

IV
Experimental: 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
Arzneimittel: Silmitasertib

Capsules

Andere Namen:
  • CX-4945
Arzneimittel: Irinotecan

IV

Arzneimittel: Temozolomide

Oral or IV

Arzneimittel: Vincristine

IV
Experimental: Phase II- Relapsed/refractory Neuroblastoma

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

Capsules

Andere Namen:
  • CX-4945
Arzneimittel: Irinotecan

IV

Arzneimittel: Temozolomide

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

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

Capsules

Andere Namen:
  • CX-4945
Arzneimittel: Irinotecan

IV

Arzneimittel: Temozolomide

Oral or IV

Arzneimittel: Vincristine

IV

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 2 years

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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: 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
Zeitfenster: 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
Zeitfenster: 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

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

Milton S. Hershey Medical Center

Ermittler

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

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Nützliche Links

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn (Tatsächlich)

30. Oktober 2024

Primärer Abschluss (Geschätzt)

1. November 2030

Studienabschluss (Geschätzt)

1. November 2035

Studienanmeldedaten

Zuerst eingereicht

2. August 2024

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

2. August 2024

Zuerst gepostet (Tatsächlich)

7. August 2024

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

6. Oktober 2026

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

5. Oktober 2026

Zuletzt verifiziert

1. Oktober 2026

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • BCC021

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

NEIN

Arzneimittel- und Geräteinformationen, Studienunterlagen

Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt

Ja

Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt

Nein

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