Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors

September 1, 2026 updated by: Giselle Sholler, Milton S. Hershey Medical Center

Phase I/II Study of Silmitasertib (CX-4945) in Combination With Chemotherapy in Children and Young Adults With Relapsed Refractory Solid Tumors

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

104

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: Irinotecan
IV
Drug: Vincristine
IV
Drug: Silmitasertib
Capsules
Other Names:
  • CX-4945
Drug: Temozolomide
Oral or 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
Drug: Irinotecan
IV
Drug: Vincristine
IV
Drug: Silmitasertib
Capsules
Other Names:
  • CX-4945
Drug: Temozolomide
Oral or IV
Experimental: Phase II- Relapsed/refractory Neuroblastoma
Silmitasertib RP2D twice a day plus Irinotecan and Temozolomide
Drug: Irinotecan
IV
Drug: Silmitasertib
Capsules
Other Names:
  • CX-4945
Drug: Temozolomide
Oral or IV
Experimental: Phase II- Relapsed/refractory Ewing sarcoma
Silmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide
Drug: Irinotecan
IV
Drug: Vincristine
IV
Drug: Silmitasertib
Capsules
Other Names:
  • CX-4945
Drug: Temozolomide
Oral or IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 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
Time Frame: 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
Time Frame: 2 years
To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts, based upon Overall response rate (ORR)
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with progression free survival (PFS) during study
Time Frame: 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- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Time Frame: 2 years plus 30 days
To characterize the safety profile of silmitasertib in combination with chemotherapy
2 years plus 30 days
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
Time Frame: 2 years
To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Overall response rate (ORR)
2 years
Phase II- Length of time that participants experience Overall Survival (OS)
Time Frame: 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 - Determine the Disease Control Rate (DCR) of participants based on response
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 30, 2024

Primary Completion (Estimated)

November 1, 2030

Study Completion (Estimated)

November 1, 2035

Study Registration Dates

First Submitted

August 2, 2024

First Submitted That Met QC Criteria

August 2, 2024

First Posted (Actual)

August 7, 2024

Study Record Updates

Last Update Posted (Actual)

September 3, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BCC021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe