The CATSINDO Trial - Clinical and Translational Study in Newly Diagnosed Osteosarcoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 46
- 试验地点
- 8
- 主要终点
- Incidence of Dose Limiting Toxicity (DLT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 7 Years 至 22 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 m
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: High-dose Methotrexate (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicity (DLT)
时间窗: Within 7-days post-discharge of methotrexate visit
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
次要结局
- Length of Stay (LOS)(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))
- Patient Cost Per Visit(Approximately 30 weeks per participant from first week of treatment)