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NeuroblastomaPhase 1/2NCT06541262

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

A Phase 1/2 study testing Silmitasertib, Irinotecan and Temozolomide in people with Neuroblastoma and Ewing Sarcoma, run by Milton S. Hershey Medical Center at 24 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Neuroblastoma, Ewing Sarcoma, Osteosarcoma
What is being tested?
Silmitasertib, Irinotecan and Temozolomide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
104 participants
Where
24 sitesin 2 countries
Study dates
30 Oct 2024to 1 Nov 2035
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age: Less than 30 years old at initial diagnosis
  • 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
  • Tumor assessment:
Show all 41Show fewer
  • Disease assessment is required for eligibility and must be done after last dose of previous therapy and prior to first dose of study drug.
  • 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:
  • Any age with International Neuroblastoma Risk Group (INRG) Stage L2, MS, or M with MYCN amplification
  • Age ≥ 547 days and INRG Stage M regardless of biologic features
  • Any age initially diagnosed with INRG Stage L1 MYCN amplified NBL who have progressed to Stage M without systemic chemotherapy
  • 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.
  • 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
  • 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:
  • Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study.
  • Small Molecule Inhibitors (anti-neoplastic agent): At least 2 weeks from the completion of therapy with a small molecule inhibitor.
  • 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.).
  • Radiotherapy: At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
  • Stem Cell Transplant:
  • Allogeneic: No evidence of active graft vs. host disease
  • Allogeneic/Autologous: ≥ 2 months must have elapsed since transplant.
  • MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
  • Subjects must have a Lansky or Karnofsky Performance Scale score of >/= 50.
  • 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
  • Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.
  • Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).

Who cannot join

  • Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
  • 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.
  • Subjects who are currently receiving Vitamin K antagonists (warfarin).
  • Subjects who are currently receiving the class of lipid-lowering medications HMG-CoA reductase inhibitors (statins).
  • 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.
  • 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.
Show all 14Show fewer
  • 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.
  • Subjects with any of the following gastrointestinal disorders:
  • Active malabsorption (e.g. short gut) syndrome.
  • Uncontrolled diarrhea (excess of 4 stools/day)
  • Gastritis, ulcerative colitis, Chron's disease or hemorrhagic coloproctitis
  • History of gastric or small bowel surgery involving any extent of gastric or small bowel resection
  • 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.)
  • Subjects with a history of any other malignancy.

Trial locations and contacts

24 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

BCC Enroll contact

7175310003

BCCEnroll@pennstatehealth.psu.edu

24 sites in 2 countries

United States23 sites, 23 recruiting

  • University of Alabama/Children's of Alabama

    Birmingham, Alabama, 35233

    Bridget Tate, btate@peds.uab.edu

    Elizabeth Alva

    Recruiting

  • Children's Medical Center

    Dallas, Texas, 75235

    Rachel Nam, rachel.nam@childrens.com

    Tanya Watt

    Recruiting

  • Children's Hospital of Michigan/Wayne State University

    Detroit, Michigan, 48201

    Audrey Brennan, brenn1a@cmich.edu

    Alissa Martin

    Recruiting

  • University of Florida

    Gainesville, Florida, 32611

    Ashley Bayne, abayne@ufl.edu

    Joanne Lagmay

    Recruiting

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Kellie Daniel, kellie.danielle@hmhn.org

    Katharine Offer

    Recruiting

  • Connecticut Children's Hospital

    Hartford, Connecticut, 06106

    Adam Barselau, Abarselau@connecticutchildrens.org

    Michael Isakoff

    Recruiting

  • Penn State Milton S. Hershey Medical Center and Children's Hospital

    Hershey, Pennsylvania, 17033

    Suzanne Treadway, streadway@hmc.psu.edu

    Valerie Brown

    Recruiting

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96813

    Andrea Siu, MPH, andrea.siu@kapiolani.org

    Kelley Hutchins

    Recruiting

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

    Nicole Harvey, ndharvey@cmh.edu

    Kevin Ginn

    Recruiting

  • Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine

    Louisville, Kentucky, 40202

    Jennifer Miller, Jennifer.Miller4@nortonhealthcare.org

    Michael Ferguson

    Recruiting

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

    Aixa Guadarrama, Aixa.Guadarrama@Nicklaushealth.org

    Maggie Fader

    Recruiting

  • Monroe Carrell Jr. Children's Hospital at Vanderbilt

    Nashville, Tennessee, 37232

    Aida Constantinescu, aida.constantinescu@vumc.org

    Daniel Benedetti

    Recruiting

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

    Group Contact, pedsoncrschoak@ucsf.edu

    Jennifer Michlitsch

    Recruiting

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

    Marie Frankos, marie.frankos@orlandohealth.com

    Jaime Libes-Bander

    Recruiting

  • Phoenix Children's Hospital

    Phoenix, Arizona, 85016

    Brianna Lent, blent@phoenixchildrens.com

    Francis Eshun

    Recruiting

  • Hasbro Children's Hospital

    Providence, Rhode Island, 02903

    Christopher Bouressa, cbouressa@lifespan.org

    Bradley DeNardo

    Recruiting

  • Virginia Commonwealth University

    Richmond, Virginia, 23284

    Mary Madu, memadu@vcu.edu

    Madhu Gowda

    Recruiting

  • UC Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Mary Gay Lapasaran, mlapasaran@health.ucdavis.edu

    Marcio Malogolowkin

    Recruiting

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

    Group Contact, Pc-cog@imail.org

    Matthew Dietz

    Recruiting

  • Rady Children's Hospital

    San Diego, California, 92123

    Megan Saenz, msaenz@rchsd.org

    William Roberts

    Recruiting

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

    Gina Martin, gina.martin@health.slu.edu

    William Ferguson

    Recruiting

  • All Children's Hospital Johns Hopkins Medicine

    St. Petersburg, Florida, 33701

    Kevin Samnarine, ksamnar1@jh.edu

    Jennifer Dean

    Recruiting

  • St. Joseph's Children's Hospital

    Tampa, Florida, 33614

    Jennifer Manns, RN, jennifer.manns@baycare.org

    Don Eslin

    Recruiting

Other trials in United States

Canada1 site, 1 recruiting

  • UHC Sainte-Justine

    Montreal, Quebec, QC H3S 2G4

    Karyne Daigle, karyne.daigle.hsj@ssss.quov.qc.ca

    Monia Marzouki

    Recruiting

Other trials in Canada

About this study

Official title: 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
Being tested
Silmitasertib, Irinotecan, Temozolomide, Vincristine
Medical subject headings
Neuroblastoma, Sarcoma, Ewing, Osteosarcoma, Rhabdomyosarcoma, Liposarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06541262
Study groupRoleWhat they receive
Phase I- Dose level 1ExperimentalSilmitasertib 600 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Receives: Drug: Silmitasertib; Drug: Irinotecan; Drug: Temozolomide; Drug: Vincristine
Phase I- Dose level 2ExperimentalSilmitasertib 800 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Receives: Drug: Silmitasertib; Drug: Irinotecan; Drug: Temozolomide; Drug: Vincristine
Phase II- Relapsed/refractory NeuroblastomaExperimentalSilmitasertib RP2D twice a day plus Irinotecan and Temozolomide
Receives: Drug: Silmitasertib; Drug: Irinotecan; Drug: Temozolomide
Phase II- Relapsed/refractory Ewing sarcomaExperimentalSilmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide
Receives: Drug: Silmitasertib; Drug: Irinotecan; Drug: Temozolomide; Drug: Vincristine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    To characterize the safety profile of silmitasertib in combination with chemotherapy

    Measured: 2 years plus 30 days

  2. Phase I- Number of Participants with Dose Limiting Toxicities to determine RP2D

    To determine the Recommended Phase 2 Dose (RP2D) of silmitasertib in combination with chemotherapy

    Measured: 21 days

  3. Phase II- Determine the Overall Response Rate (ORR) of Participants using INRC

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

    Measured: 2 years

Secondary outcomes (5)

  1. Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC

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

    Measured: 2 years

  2. Number of participants with progression free survival (PFS) during study

    To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Progression Free Survival (PFS)

    Measured: 2 years

  3. Phase II- Length of time that participants experience Overall Survival (OS)

    To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts based upon Overall Survival (OS)

    Measured: 7 years

  4. Phase II- Number of Participants with Adverse Events as a Measure of Safety and Tolerability

    To characterize the safety profile of silmitasertib in combination with chemotherapy

    Measured: 2 years plus 30 days

  5. Phase II - Determine the Disease Control Rate (DCR) of participants based on response

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

    Measured: 2 years plus 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2024
  2. Study start30 Oct 2024
  3. Primary completion1 Nov 2030 (estimated)
  4. Study completion1 Nov 2035 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
104 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06541262
Sponsor's protocol ID
BCC021
Status last verified
Oct 2026
First submitted
2 Aug 2024
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Silmitasertib, Irinotecan and Temozolomide in people with Neuroblastoma and Ewing Sarcoma, run by Milton S. Hershey Medical Center at 24 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact BCC Enroll (7175310003, BCCEnroll@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability (time frame: 2 years plus 30 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06541262.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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