Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
Phase I/II Study of Silmitasertib (CX-4945) in Combination With Chemotherapy in Children and Young Adults With Relapsed Refractory Solid Tumors
1 other identifier
interventional
104
2 countries
21
Brief 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. 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2024
Longer than P75 for phase_1
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 2, 2024
CompletedFirst Posted
Study publicly available on registry
August 7, 2024
CompletedStudy Start
First participant enrolled
October 30, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
November 1, 2035
April 9, 2026
April 1, 2026
6 years
August 2, 2024
April 7, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
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
2 years plus 30 days
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
21 days
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)
2 years
Secondary Outcomes (5)
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
2 years
Number of participants with progression free survival (PFS) during study
2 years
Phase II- Length of time that participants experience Overall Survival (OS)
7 years
Phase II- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
2 years plus 30 days
Phase II - Determine the Disease Control Rate (DCR) of participants based on response
2 years plus 30 days
Study Arms (4)
Phase I- Dose level 1
EXPERIMENTALSilmitasertib 600 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Phase I- Dose level 2
EXPERIMENTALSilmitasertib 800 mg/m2 twice a day plus Neuroblastoma: Regimen A: Irinotecan and Temozolomide Sarcoma: Regimen B: Vincristine, Irinotecan and Temozolomide
Phase II- Relapsed/refractory Neuroblastoma
EXPERIMENTALSilmitasertib RP2D twice a day plus Irinotecan and Temozolomide
Phase II- Relapsed/refractory Ewing sarcoma
EXPERIMENTALSilmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide
Interventions
Capsules
IV
Oral
IV
Eligibility Criteria
You may qualify if:
- 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:
- 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
- +24 more criteria
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
University of Alabama/Children's of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
Rady Children's Hospital
San Diego, California, 92123, United States
University of Florida
Gainesville, Florida, 32611, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
All Children's Hospital Johns Hopkins Medicine
St. Petersburg, Florida, 33701, United States
St. Joseph's Children's Hospital
Tampa, Florida, 33614, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96813, United States
Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
Louisville, Kentucky, 40202, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
Penn State Milton S. Hershey Medical Center and Children's Hospital
Hershey, Pennsylvania, 17033, United States
Hasbro Children's Hospital
Providence, Rhode Island, 02903, United States
Monroe Carrell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, 37232, United States
Children's Medical Center
Dallas, Texas, 75235, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Virginia Commonwealth University
Richmond, Virginia, 23284, United States
UHC Sainte-Justine
Montreal, Quebec, QC H3S 2G4, Canada
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Chandrika Behura, MD
Penn State Health Children's Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Beat Childhood Cancer Chair
Study Record Dates
First Submitted
August 2, 2024
First Posted
August 7, 2024
Study Start
October 30, 2024
Primary Completion (Estimated)
November 1, 2030
Study Completion (Estimated)
November 1, 2035
Last Updated
April 9, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share