이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

재발성 난치성 고형 종양에 대한 화학요법과 병용하는 실미타서팁(CX-4945)

2026년 10월 5일 업데이트: Giselle Sholler, Milton S. Hershey Medical Center

재발성 난치성 고형 종양이 있는 소아 및 청소년을 대상으로 화학요법과 병용한 Silmitasertib(CX-4945)의 I/II상 연구

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

연구 개요

상태

모병

정황

개입 / 치료

연구 유형

중재적

등록 (추정된)

104

단계

  • 2 단계
  • 1단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

30년 이하 (어린이, 성인)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위화되지 않음
  • 중재 모델: 순차적 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: 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
의약품: Silmitasertib

Capsules

다른 이름들:
  • CX-4945
의약품: Irinotecan

IV

의약품: Temozolomide

Oral or IV

의약품: Vincristine

IV
실험적: 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
의약품: Silmitasertib

Capsules

다른 이름들:
  • CX-4945
의약품: Irinotecan

IV

의약품: Temozolomide

Oral or IV

의약품: Vincristine

IV
실험적: Phase II- Relapsed/refractory Neuroblastoma

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

Capsules

다른 이름들:
  • CX-4945
의약품: Irinotecan

IV

의약품: Temozolomide

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

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

Capsules

다른 이름들:
  • CX-4945
의약품: Irinotecan

IV

의약품: Temozolomide

Oral or IV

의약품: Vincristine

IV

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
기간: 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
기간: 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
기간: 2 years

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

2차 결과 측정

결과 측정
측정값 설명
기간
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
기간: 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
기간: 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)
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Milton S. Hershey Medical Center

수사관

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

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

유용한 링크

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2024년 10월 30일

기본 완료 (추정된)

2030년 11월 1일

연구 완료 (추정된)

2035년 11월 1일

연구 등록 날짜

최초 제출

2024년 8월 2일

QC 기준을 충족하는 최초 제출

2024년 8월 2일

처음 게시됨 (실제)

2024년 8월 7일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 10월 6일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 10월 5일

마지막으로 확인됨

2026년 10월 1일

추가 정보

이 연구와 관련된 용어

추가 관련 MeSH 약관

기타 연구 ID 번호

  • BCC021

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다