RECRUITING

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

Conditions

Neuroblastoma Recurrent Ewing's Sarcoma Recurrent Osteosarcoma Recurrent Rhabdomyosarcoma Recurrent Liposarcoma Recurrent

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

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

Quick Facts

Study Start:2024-10-30

Study Completion:2035-11-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06541262

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.

Ages Eligible for Study:Not specified to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion 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 * Relapsed/refractory Neuroblastoma * Relapsed/refractory Ewing sarcoma 3. Tumor assessment: 4. Disease Status: 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 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: 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. Subject must be able to swallow capsules. 9. Subjects must have adequate organ function at the time of enrollment: * Cardiac- Corrected QT (QTc) interval \<480ms (calculated using Bazett formula) * 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 Creatinine clearance (in units ml/min) or radioisotope GFR ≥ 70. 10. Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy. 11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).	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. Difficulty with swallowing or 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.

Inclusion Criteria

Exclusion 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
* Relapsed/refractory Neuroblastoma
* Relapsed/refractory Ewing sarcoma
3. Tumor assessment:
4. Disease Status:
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
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:
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. Subject must be able to swallow capsules.
9. Subjects must have adequate organ function at the time of enrollment:
* Cardiac- Corrected QT (QTc) interval \<480ms (calculated using Bazett formula)
* 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 Creatinine clearance (in units ml/min) or radioisotope GFR ≥ 70.
10. Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.
11. Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).

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. Difficulty with swallowing or 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.

Contacts and Locations

Study Contact

BCC Enroll

CONTACT

7175310003

BCCEnroll@pennstatehealth.psu.edu

Principal Investigator

Chandrika Behura, MD

STUDY_CHAIR

Penn State Health Children's Hospital

Study Locations (Sites)

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

Hershey, Pennsylvania, 17033

United States

Collaborators and Investigators

Sponsor: Milton S. Hershey Medical Center

Chandrika Behura, MD, STUDY_CHAIR, Penn State Health Children's Hospital

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 Registration Dates

Study Start Date2024-10-30

Study Completion Date2035-11-01

Study Record Updates

Study Start Date2024-10-30

Study Completion Date2035-11-01

Terms related to this study

Additional Relevant MeSH Terms

Neuroblastoma Recurrent
Ewing's Sarcoma Recurrent
Osteosarcoma Recurrent
Rhabdomyosarcoma Recurrent
Liposarcoma Recurrent