The CATSINDO Trial - Clinical and Translational Study in Newly Diagnosed Osteosarcoma
The goal of this study is to learn whether children, adolescents, and young adults with newly diagnosed high-grade osteosarcoma can be safely discharged from the hospital at slightly higher methotrexate blood levels after receiving standard high-dose methotrexate chemotherapy. Participants are 22 years old or younger and are receiving standard MAP (high-dose methotrexate with doxorubicin and cisplatin) chemotherapy as part of their routine cancer treatment.
The main questions this study aims to answer are:
- Is hospital discharge at higher methotrexate levels safe, based on side effects or hospital re-admission within 7 days?
- Can patient-derived osteosarcoma tumor organoids be successfully generated across multiple centers?
Researchers will compare safety outcomes and hospital length of stay to historical patient data discharged at lower methotrexate levels.
Participants will receive standard chemotherapy, meet study-defined discharge criteria, be monitored for side effects, and have the option to provide tumor and blood samples for future research.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
This Phase II, multi-institutional study evaluates the safety of hospital discharge at higher serum methotrexate (MTX) levels in children, adolescents, and young adults with newly diagnosed high-grade osteosarcoma receiving standard-of-care high-dose methotrexate (HD-MTX) as part of MAP chemotherapy.
Participants are discharged once they meet the pre-defined MTX clearance, kidney function, and clinical safety criteria. Methotrexate discharge thresholds are evaluated using an adaptive Bayesian threshold-finding design, starting at a serum MTX level of less than or equal to 0.15 micromolar, with possible escalation or de-escalation based on observed toxicity.
Secondary objectives include comparison of hospital length of stay and estimated inpatient costs with historical controls using traditional discharge criteria. Optional correlative studies include patient-derived osteosarcoma tumor organoids and circulating tumor cells to evaluate chemotherapy sensitivity and other future research. A separate retrospective chart review of prior patients treated with HD-MTX is included to understand safety outcomes and MTX clearance patterns.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiekontakt
- Navn: Heather Neagle
- Telefonnummer: 980-442-2303
- E-post: heather.neagle@advocatehealth.org
Studiesteder
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North Carolina
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Chapel Hill, North Carolina, Forente stater, 27599
- University of North Carolina at Chapel Hill
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Ta kontakt med:
- Juanita Cuffree, MPH
- Telefonnummer: 919-966-0017
- E-post: cuffree@med.unc.edu
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Hovedetterforsker:
- Ian Davis, MD, PhD
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Charlotte, North Carolina, Forente stater, 28204
- Novant Health Hemby Children's Hospital
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Hovedetterforsker:
- Jessica Bell, MD
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Ta kontakt med:
- Eliana Sanchez-Ocampo
- Telefonnummer: 704-384-1199
- E-post: Eliana.Sanchez@novanthealth.org
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Durham, North Carolina, Forente stater, 27710
- Duke University Medical Center
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Hovedetterforsker:
- Jessica Sun, MD
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Ta kontakt med:
- Morgan Low, MSW
- Telefonnummer: 919-613-1895
- E-post: morgan.low@duke.edu
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Greenville, North Carolina, Forente stater, 27834
- East Carolina University
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Ta kontakt med:
- Tori Donadio, MPH
- Telefonnummer: 252-744-2301
- E-post: donadiov21@ecu.edu
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Hovedetterforsker:
- Andrea Whitfield, DO
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Winston-Salem, North Carolina, Forente stater, 27157
- Atrium Health Wake Forest Baptist
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Hovedetterforsker:
- Sarah Supples, MD
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Ta kontakt med:
- Nicole Johnson, BS
- Telefonnummer: 336-702-4498
- E-post: nicole.johnson3@advocatehealth.org
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South Carolina
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Charleston, South Carolina, Forente stater, 29425
- Medical University of South Carolina
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Hovedetterforsker:
- Jacqueline Kraveka, DO
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Ta kontakt med:
- Monica Martino
- Telefonnummer: 843-792-1465
- E-post: cto-peds-onc@musc.edu
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Columbia, South Carolina, Forente stater, 29203
- Prisma Health Midlands
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Ta kontakt med:
- Carrie Ross, RN, BSN
- Telefonnummer: 803-434-7099
- E-post: Carrie.Ross@PrismaHealth.org
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Hovedetterforsker:
- Chandni Dargan, MD
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Greenville, South Carolina, Forente stater, 29605
- Prisma Health Upstate
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Hovedetterforsker:
- Chandni Dargan, MD
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Ta kontakt med:
- Tranaka Fuqua, MBA, CCRP, BSN, RN
- Telefonnummer: 864-455-5158
- E-post: Tranaka.Fuqua@prismahealth.org
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
Tar imot friske frivillige
Beskrivelse
Pre-Enrollment Criteria:
- Suspected diagnosis of high-grade osteosarcoma based on clinical and radiographic findings.
- Informed consent (and assent, if applicable) obtained, per institutional guidelines.
- Participants must be ≤ 22 years of age at the time of consent.
Inclusion Criteria:
- Participants with localized or metastatic high-grade osteosarcoma.
- Participants must be ≤ 22 years of age at the time of consent.
- Participants must have a body surface area of greater than or equal to 0.8 m2.
Participants receiving or planning to receive induction/neoadjuvant MAP chemotherapy with HD-MTX given at the standard dose of 12 gm/m2 (maximum 20 gm).
NOTE: Participants may be participating on other clinical studies such as the COG trial AOST2032 or any other clinical trial as long as their treatment includes MAP chemotherapy with the standard HD-MTX dose of 12 gm/m2 (maximum 20 gm).
- Participants may receive other chemotherapy agents in their treatment provided that drug(s) are not known to interfere with HD-MTX clearance when given concurrently. Medications known to interfere with HD-MTX clearance are listed in Appendix A.
Participants must meet minimum organ function requirements to receive HD-MTX:
- Adequate liver function defined as: total bilirubin ≤ 1.5x upper limit of normal (ULN) for age at the time of consent and alanine aminotransferase (ALT/SGPT) ≤ 135 U/L for age at the time of consent.
- Adequate renal function defined as: a serum creatinine based on age/gender OR - a 24-hour urine Creatinine clearance ≥ 70 mL/min/1.73 m2, OR - an estimated glomerular filtration rate (GFR) of greater than or equal to 70 mL/min/1.73 m2 for age at the time of consent.
- Adequate bone marrow function defined as: peripheral absolute neutrophil count (ANC) ≥ 1000/µL, platelet count ≥ 100,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment), and hemoglobin ≥ 8.0 g/dL (transfusion independent, defined as not receiving red blood cell transfusions within a 7-day period prior to enrollment)
Adequate cardiac function, defined as a left ventricular ejection fraction (LVEF) ≥ 50%, assessed per institutional standard of care using non-invasive imaging modalities such as a Multi-Gated Acquisition (MUGA) scan or echocardiogram (echo).
NOTE: Cardiac function assessment will be performed as part of routine clinical care. No additional imaging or procedures will be mandated by the research protocol.
- Informed consent, and assent when appropriate, must be obtained, per institutional guidelines.
- Participants can enroll after initiation of induction MAP chemotherapy so long as they are enrolled prior to the second cycle of chemotherapy (prior to week 6 cisplatin and doxorubicin).
- Participants must be willing and able to comply with all study procedures for the entire length of the study.
Exclusion Criteria:
Female participants who are pregnant and/or lactating and breast feeding their infant(s).
NOTE: Pregnancy testing will follow institutional standard of care practice and is not mandated by the protocol.
- Sexually active participants of reproductive potential who have not agreed to use an effective contraceptive method for the duration of protocol therapy, at the discretion of the investigator.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Støttende omsorg
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Standard-of-Care MAP Chemotherapy with Threshold-Adjusted HD-MTX Discharge
Participants with newly diagnosed high-grade osteosarcoma receive standard-of-care MAP chemotherapy, including high-dose methotrexate (HD-MTX), with hospital discharge based on serum methotrexate threshold levels (ranging from ≤0.10 µM to ≤0.20 µM) and renal function criteria to evaluate the safety of earlier discharge.
Threshold levels are not randomized and are evaluated sequentially over the course of the study.
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High-dose methotrexate (HD-MTX) is administered intravenously at a dose of 12 g/m² (maximum dose 20 g) over 4 hours as part of standard-of-care MAP chemotherapy for participants with newly diagnosed high-grade osteosarcoma.
HD-MTX is delivered with standard supportive care measures, including alkalinized intravenous hydration, serial serum methotrexate level monitoring, and leucovorin rescue beginning 24 hours after methotrexate initiation and continued until discharge criteria are met.
Treatment is administered according to institutional standards throughout neoadjuvant/induction and adjuvant/consolidation therapy.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Incidence of Dose Limiting Toxicity (DLT)
Tidsramme: Within 7-days post-discharge of methotrexate visit
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A binary response for dose-limiting toxicity following MTX visit discharge defined as rehospitalization due to acute toxicity or serious adverse event of special interest
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Within 7-days post-discharge of methotrexate visit
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Length of Stay (LOS)
Tidsramme: From time of admission to time of discharge in hours for each HD-MTX inpatient cycle, assessed across [up to] 12 cycles per participant, through completion of HD-MTX therapy (up to approximately 30 weeks per participant from first week of treatment)
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Length of hospital stay measured in hours from time of admission to time of discharge for each HD-MTX inpatient cycle
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From time of admission to time of discharge in hours for each HD-MTX inpatient cycle, assessed across [up to] 12 cycles per participant, through completion of HD-MTX therapy (up to approximately 30 weeks per participant from first week of treatment)
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Patient Cost Per Visit
Tidsramme: Approximately 30 weeks per participant from first week of treatment
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Total estimated cost associated with each HD-MTX inpatient cycle, based on hospital billing charges and nights of stay
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Approximately 30 weeks per participant from first week of treatment
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Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Thomas Russell, MD, Alliance for Research and Innovations in Pediatric Oncology (ARISE) Cancer Consortium
Studierekorddatoer
Studer hoveddatoer
Studiestart (Antatt)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- Pro00081644 (Advarra IRB)
- ARISE-CATSINDO (Annen identifikator: Alliance for Research and Innovations in Pediatric Oncology (ARISE) Cancer Consortium)
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