Silmitasertib (CX-4945) en combinación con quimioterapia para tumores sólidos refractarios en recaída
Estudio de fase I/II de Silmitasertib (CX-4945) en combinación con quimioterapia en niños y adultos jóvenes con tumores sólidos refractarios en recaída
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
Descripción general del estudio
Estado
Intervención / Tratamiento
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: BCC Enroll
- Número de teléfono: 7175310003
- Correo electrónico: BCCEnroll@pennstatehealth.psu.edu
Ubicaciones de estudio
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Quebec
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Montreal, Quebec, Canadá, QC H3S 2G4
- Reclutamiento
- UHC Sainte-Justine
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Investigador principal:
- Monia Marzouki
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Contacto:
- Karyne Daigle
- Correo electrónico: karyne.daigle.hsj@ssss.quov.qc.ca
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Alabama
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Birmingham, Alabama, Estados Unidos, 35233
- Reclutamiento
- University of Alabama/Children's of Alabama
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Contacto:
- Bridget Tate
- Correo electrónico: btate@peds.uab.edu
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Investigador principal:
- Elizabeth Alva
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Arizona
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Phoenix, Arizona, Estados Unidos, 85016
- Reclutamiento
- Phoenix Children's Hospital
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Contacto:
- Brianna Lent
- Correo electrónico: blent@phoenixchildrens.com
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Investigador principal:
- Francis Eshun
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California
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Oakland, California, Estados Unidos, 94609
- Reclutamiento
- UCSF Benioff Children's Hospital Oakland
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Investigador principal:
- Jennifer Michlitsch
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Contacto:
- Group Contact
- Correo electrónico: pedsoncrschoak@ucsf.edu
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Sacramento, California, Estados Unidos, 95817
- Reclutamiento
- UC Davis Comprehensive Cancer Center
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Contacto:
- Mary Gay Lapasaran
- Correo electrónico: mlapasaran@health.ucdavis.edu
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Investigador principal:
- Marcio Malogolowkin
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San Diego, California, Estados Unidos, 92123
- Reclutamiento
- Rady Children's Hospital
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Contacto:
- Megan Saenz
- Correo electrónico: msaenz@rchsd.org
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Investigador principal:
- William Roberts
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Connecticut
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Hartford, Connecticut, Estados Unidos, 06106
- Reclutamiento
- Connecticut Children's Hospital
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Contacto:
- Adam Barselau
- Correo electrónico: Abarselau@connecticutchildrens.org
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Investigador principal:
- Michael Isakoff
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Florida
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Gainesville, Florida, Estados Unidos, 32611
- Reclutamiento
- University of Florida
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Investigador principal:
- Joanne Lagmay
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Contacto:
- Ashley Bayne
- Correo electrónico: abayne@ufl.edu
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Miami, Florida, Estados Unidos, 33155
- Reclutamiento
- Nicklaus Children's Hospital
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Contacto:
- Aixa Guadarrama
- Correo electrónico: Aixa.Guadarrama@Nicklaushealth.org
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Investigador principal:
- Maggie Fader
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Orlando, Florida, Estados Unidos, 32806
- Reclutamiento
- Arnold Palmer Hospital for Children
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Contacto:
- Marie Frankos
- Correo electrónico: marie.frankos@orlandohealth.com
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Investigador principal:
- Jaime Libes-Bander
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St. Petersburg, Florida, Estados Unidos, 33701
- Reclutamiento
- All Children's Hospital Johns Hopkins Medicine
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Contacto:
- Kevin Samnarine
- Correo electrónico: ksamnar1@jh.edu
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Investigador principal:
- Jennifer Dean
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Tampa, Florida, Estados Unidos, 33614
- Reclutamiento
- St. Joseph's Children's Hospital
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Investigador principal:
- Don Eslin
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Contacto:
- Jennifer Manns, RN
- Correo electrónico: jennifer.manns@baycare.org
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Hawaii
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Honolulu, Hawaii, Estados Unidos, 96813
- Reclutamiento
- Kapiolani Medical Center for Women and Children
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Contacto:
- Andrea Siu, MPH
- Correo electrónico: andrea.siu@kapiolani.org
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Investigador principal:
- Kelley Hutchins
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Kentucky
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Louisville, Kentucky, Estados Unidos, 40202
- Reclutamiento
- Norton Children's Research Institute/Affiliated with University of Louisville School of Medicine
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Investigador principal:
- Michael Ferguson
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Contacto:
- Jennifer Miller
- Correo electrónico: Jennifer.Miller4@nortonhealthcare.org
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Reclutamiento
- Children's Hospital of Michigan/Wayne State University
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Contacto:
- Audrey Brennan
- Correo electrónico: brenn1a@cmich.edu
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Investigador principal:
- Alissa Martin
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Missouri
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Kansas City, Missouri, Estados Unidos, 64108
- Reclutamiento
- Children's Mercy Hospitals and Clinics
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Investigador principal:
- Kevin Ginn
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Contacto:
- Nicole Harvey
- Correo electrónico: ndharvey@cmh.edu
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St Louis, Missouri, Estados Unidos, 63104
- Reclutamiento
- Cardinal Glennon Children's Medical Center
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Investigador principal:
- William Ferguson
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Contacto:
- Gina Martin
- Correo electrónico: gina.martin@health.slu.edu
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New Jersey
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Hackensack, New Jersey, Estados Unidos, 07601
- Reclutamiento
- Hackensack University Medical Center
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Investigador principal:
- Katharine Offer
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Contacto:
- Kellie Daniel
- Correo electrónico: kellie.danielle@hmhn.org
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Pennsylvania
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Hershey, Pennsylvania, Estados Unidos, 17033
- Reclutamiento
- Penn State Milton S. Hershey Medical Center and Children's Hospital
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Contacto:
- Suzanne Treadway
- Correo electrónico: streadway@hmc.psu.edu
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Investigador principal:
- Valerie Brown
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Rhode Island
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Providence, Rhode Island, Estados Unidos, 02903
- Reclutamiento
- Hasbro Children's Hospital
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Investigador principal:
- Bradley DeNardo
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Contacto:
- Christopher Bouressa
- Correo electrónico: cbouressa@lifespan.org
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Tennessee
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Nashville, Tennessee, Estados Unidos, 37232
- Reclutamiento
- Monroe Carrell Jr. Children's Hospital at Vanderbilt
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Contacto:
- Aida Constantinescu
- Correo electrónico: aida.constantinescu@vumc.org
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Investigador principal:
- Daniel Benedetti
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Texas
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Dallas, Texas, Estados Unidos, 75235
- Reclutamiento
- Children's Medical Center
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Investigador principal:
- Tanya Watt
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Contacto:
- Rachel Nam
- Correo electrónico: rachel.nam@childrens.com
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Utah
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Salt Lake City, Utah, Estados Unidos, 84113
- Reclutamiento
- Primary Children's Hospital
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Investigador principal:
- Matthew Dietz
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Contacto:
- Group Contact
- Correo electrónico: Pc-cog@imail.org
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Virginia
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Richmond, Virginia, Estados Unidos, 23284
- Reclutamiento
- Virginia Commonwealth University
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Contacto:
- Mary Madu
- Correo electrónico: memadu@vcu.edu
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Investigador principal:
- Madhu Gowda
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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Age: Less than 30 years old at initial diagnosis
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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
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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.
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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.
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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
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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:
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Myelosuppressive chemotherapy: Must not have received within 2 weeks of enrollment onto this study.
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Small Molecule Inhibitors (anti-neoplastic agent): At least 2 weeks from the completion of therapy with a small molecule inhibitor.
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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.).
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Radiotherapy: At least 30 days since the last treatment except for radiation delivered with palliative intent to a non-target site.
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Stem Cell Transplant:
- Allogeneic: No evidence of active graft vs. host disease
- Allogeneic/Autologous: ≥ 2 months must have elapsed since transplant.
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MIBG Therapy: At least 6 weeks since treatment with MIBG therapy.
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Subjects must have a Lansky or Karnofsky Performance Scale score of >/= 50.
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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
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Subjects of childbearing potential must have a negative serum pregnancy test. Subjects of childbearing potential must agree to use effective measures to avoid pregnancy.
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Written informed consent in accordance with institutional and FDA guidelines must be obtained from all subjects (or subjects' legal representative).
Exclusion Criteria:
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Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
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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.
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Subjects who are currently receiving Vitamin K antagonists (warfarin).
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Subjects who are currently receiving the class of lipid-lowering medications HMG-CoA reductase inhibitors (statins).
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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.
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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.
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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.
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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
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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.)
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Subjects with a history of any other malignancy.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación Secuencial
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
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 |
Capsules
Otros nombres:
IV Oral or IV 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 |
Capsules
Otros nombres:
IV Oral or IV IV |
|
Experimental: Phase II- Relapsed/refractory Neuroblastoma
Silmitasertib RP2D twice a day plus Irinotecan and Temozolomide |
Capsules
Otros nombres:
IV Oral or IV |
|
Experimental: Phase II- Relapsed/refractory Ewing sarcoma
Silmitasertib RP2D twice a day plus Vincristine, irinotecan and temozolomide |
Capsules
Otros nombres:
IV Oral or IV IV |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase I- Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Periodo de tiempo: 2 years plus 30 days
|
To characterize the safety profile of silmitasertib in combination with chemotherapy |
2 years plus 30 days
|
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Phase I- Number of Participants with Dose Limiting Toxicities to determine RP2D
Periodo de tiempo: 21 days
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To determine the Recommended Phase 2 Dose (RP2D) of silmitasertib in combination with chemotherapy |
21 days
|
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Phase II- Determine the Overall Response Rate (ORR) of Participants using INRC
Periodo de tiempo: 2 years
|
To evaluate the efficacy of silmitasertib in combination with chemotherapy in 2 disease cohorts, based upon Overall response rate (ORR) |
2 years
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Phase I- Determine the Overall Response Rate (ORR) of Participants using INRC
Periodo de tiempo: 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
Periodo de tiempo: 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)
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: 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
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Silla de estudio: Chandrika Behura, MD, Penn State Health Children's Hospital
Publicaciones y enlaces útiles
Enlaces Útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Neoplasias Neuroepiteliales
- Tumores neuroectodérmicos
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Sarcoma
- Neoplasias De Tejidos Conectivos Y Blandos
- Tumores Neuroectodérmicos Primitivos Periféricos
- Tumores Neuroectodérmicos Primitivos
- Neoplasias De Tejido Óseo
- Neoplasias Del Tejido Conectivo
- Neoplasias De Tejido Muscular
- Neoplasias De Tejido Adiposo
- Miosarcoma
- Neuroblastoma
- Sarcoma de Ewing
- Liposarcoma
- Rabdomiosarcoma
- Osteosarcoma
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Azoles
- Campeptecina
- Alcaloides
- Dacarbazina
- Triazenes
- Imidazoles
- Indoles
- Alcaloides de Vinca
- Alcaloides de triptamina de secologanina
- Alcaloides de indol
- Indolizidinas
- Indolizinas
- Temozolomida
- Irinotecán
- Vincristina
- silmitasertib
Otros números de identificación del estudio
- BCC021
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .