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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：Heather Neagle
- 電話番号：980-442-2303
- メール：heather.neagle@advocatehealth.org
研究場所
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North Carolina
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Chapel Hill、North Carolina、アメリカ、27599
- University of North Carolina at Chapel Hill
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コンタクト：
- Juanita Cuffree, MPH
- 電話番号：919-966-0017
- メール：cuffree@med.unc.edu
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主任研究者：
- Ian Davis, MD, PhD
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Charlotte、North Carolina、アメリカ、28204
- Novant Health Hemby Children's Hospital
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主任研究者：
- Jessica Bell, MD
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コンタクト：
- Eliana Sanchez-Ocampo
- 電話番号：704-384-1199
- メール：Eliana.Sanchez@novanthealth.org
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Durham、North Carolina、アメリカ、27710
- Duke University Medical Center
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主任研究者：
- Jessica Sun, MD
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コンタクト：
- Morgan Low, MSW
- 電話番号：919-613-1895
- メール：morgan.low@duke.edu
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Greenville、North Carolina、アメリカ、27834
- East Carolina University
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コンタクト：
- Tori Donadio, MPH
- 電話番号：252-744-2301
- メール：donadiov21@ecu.edu
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主任研究者：
- Andrea Whitfield, DO
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Winston-Salem、North Carolina、アメリカ、27157
- Atrium Health Wake Forest Baptist
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主任研究者：
- Sarah Supples, MD
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コンタクト：
- Nicole Johnson, BS
- 電話番号：336-702-4498
- メール：nicole.johnson3@advocatehealth.org
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South Carolina
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Charleston、South Carolina、アメリカ、29425
- Medical University of South Carolina
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主任研究者：
- Jacqueline Kraveka, DO
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コンタクト：
- Monica Martino
- 電話番号：843-792-1465
- メール：cto-peds-onc@musc.edu
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Columbia、South Carolina、アメリカ、29203
- Prisma Health Midlands
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コンタクト：
- Carrie Ross, RN, BSN
- 電話番号：803-434-7099
- メール：Carrie.Ross@PrismaHealth.org
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主任研究者：
- Chandni Dargan, MD
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Greenville、South Carolina、アメリカ、29605
- Prisma Health Upstate
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主任研究者：
- Chandni Dargan, MD
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コンタクト：
- Tranaka Fuqua, MBA, CCRP, BSN, RN
- 電話番号：864-455-5158
- メール：Tranaka.Fuqua@prismahealth.org
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参加基準
適格基準
就学可能な年齢
- 子
- 大人
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：支持療法
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence of Dose Limiting Toxicity (DLT)
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Length of Stay (LOS)
時間枠：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
時間枠：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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協力者と研究者
捜査官
- 主任研究者：Thomas Russell, MD、Alliance for Research and Innovations in Pediatric Oncology (ARISE) Cancer Consortium
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- Pro00081644 (Advarra IRB)
- ARISE-CATSINDO (その他の識別子：Alliance for Research and Innovations in Pediatric Oncology (ARISE) Cancer Consortium)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
米国で製造され、米国から輸出された製品。
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