An Open-Label, Multi-Institutional Pilot Study to Assess the Use of Glucarpidase in Adult Patients With Osteosarcoma Receiving High-Dose Methotrexate
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 6
- 主要终点
- Proportion of subjects completing 4 planned doses of high dose methotrexate (HDMTX)
研究概览
简要总结
This early phase I trial studies how well glucarpidase works in reducing toxicity in patients with osteosarcoma receiving high dose methotrexate treatment. Glucarpidase may reduce the levels of methotrexate in patients' blood and lead to shorter hospitalizations and a reduction in toxicities.
详细描述
PRIMARY OBJECTIVE:
I. To determine the rate of completion of 4 planned high dose methotrexate (HDMTX) doses when glucarpidase is administered after each dose.
SECONDARY OBJECTIVES:
I. To assess the length of hospital stay (LOS) associated with methotrexate (MTX) clearance following administration of glucarpidase 24 hours after HDMTX.
II. To assess the LOS associated with all causes following administration of glucarpidase 24 hours after HDMTX.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 25 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All races and ethnic groups will be eligible
- •A minimum of 6 individuals aged >= 40 years will be enrolled. These participants are considered high-risk.
- •Eastern Cooperative Oncology Group (ECOG) performance score 0-
- •Participants must have pathologically confirmed diagnosis of osteosarcoma. Participants must be newly diagnosed and previously untreated, although initiation of doxorubicin/cisplatin prior to enrollment is permitted.
- •Participants must have a recommended treatment plan for their osteosarcoma that includes planned MTX treatment at 8-12 g/m^
- •Absolute neutrophil count (ANC) >= 1,000/mm^3 (or >= 1.0 x 10^9/L).
- •Platelet count 75,000/mm^3 (or >= 75 x 10^9/L).
- •Hemoglobin >= 8 g/dL.
- •Serum creatinine =< 1.5 x the upper limit of normal (ULN), or glomerular filtration rate (GFR) >= 60 ml/min/1.73 m^2 as calculated by the Modification of Diet in Renal Disease (MDRD) formula.
- •Total serum bilirubin =< 2 x ULN.
- •Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 2.5 x ULN.
- •Participants must be willing to use appropriate contraception for the duration of study treatment and four months after completing HDMTX therapy.
- •Ability to understand and the willingness to sign a written informed consent document.
排除标准
- •Malignant disease, other than those being treated in this study. Exceptions to this exclusion include the following:
- •Malignancies that were treated curatively and have not recurred within 2 years after completion of treatment;
- •Completely resected basal cell and squamous cell skin cancers;
- •Any malignancy considered to be indolent and that has never required therapy;
- •Completely resected carcinoma in situ of any type.
- •Participants with rapidly progressive disease or organ dysfunction that would prevent them from receiving planned HDMTX treatment regimen.
- •Previous MTX treatment at doses >= 3 g/m^
- •Previous treatment with glucarpidase.
- •Known clinically significant liver disease defined as ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, portal hypertension, or history of autoimmune hepatitis. Patients who have completed curative therapy for HCV are eligible. Patients with known history of human immunodeficiency virus (HIV) infection are eligible.
- •Participants with a history of hypersensitivity reactions to study agent or its excipients.
- •Participants with a history of hypersensitivity to Escherichia (E.)coli-derived proteins.
- •Participants with large pleural or ascitic fluid collection.
- •Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
- •Uncontrolled intercurrent illness, or psychiatric illness/social situations that, in the opinion of the investigator, would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
- •Unable or unwilling to discontinue use of agents that interact significantly with methotrexate metabolism or excretion.
研究组 & 干预措施
Treatment (glucarpidase)
Patients receive standard of care HDMTX IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. After 24 hours after the start of each HDMTX infusion, patients also receive glucarpidase IV over 5 minutes in the absence of disease progression or unacceptable toxicity.
干预措施: Glucarpidase (Drug)
Treatment (glucarpidase)
Patients receive standard of care HDMTX IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. After 24 hours after the start of each HDMTX infusion, patients also receive glucarpidase IV over 5 minutes in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
结局指标
主要结局
Proportion of subjects completing 4 planned doses of high dose methotrexate (HDMTX)
时间窗: Time from first dose of HDMTX to time of last dose of HDMTX (week 10)
Will be estimated with an exact 95% confidence interval (CI).
次要结局
- Incidence of glucarpidase hypersensitivity(From first dose of glucarpidase until 30 days after last dose of glucarpidase)
- Incidence and severity of MTX-related toxicities(From start of first planned MTX infusion to 30 days after last dose of MTX)
- Length of hospital stay (LOS) for methotrexate (MTX) clearance(Time of start of MTX administration to time of MTX =< 0.1uM sample collection for each planned MTX infusion (up to 15 days))
- LOS for all causes (excluding MTX-related AEs)(Date of admission for each planned MTX infusion to date of discharge for each planned MTX infusion (up to 15 days))
- Length of hospital stay (LOS) for methotrexate (MTX)-related adverse events (AEs)(Date of admission for each planned MTX infusion to date of discharge for each planned MTX infusion (up to 15 days))
- Percent treatment effect at resection(From start of surgery until end of surgery)
- Incidence of glucarpidase neutralizing antibodies(From first dose of glucarpidase to 30 days after last dose of glucarpidase)
- Incidence and severity of glucarpidase toxicities(From first dose of glucarpidase to 30 days after last dose of glucarpidase)
- MTX and DAMPA serum concentration (umol/L) at 4, 24, 24.5, 36, 48 and every 24 hours after the start of MTX infusion(From start of each planned MTX infusion to time when MTX =< 0.1 uM (for each planned MTX infusion) (up to 15 days))
- Proportion of glucarpidase doses (flat dose) that result in 48 hour serum MTX level < 1 uM(From first dose of glucarpidase to end of study treatment (week 10))
- Proportion of glucarpidase doses (flat dose) that result in MTX serum concentration reduction of >= 97% from hour 24 to hour 24.5(From first dose of glucarpidase to end of study treatment (week 10))
研究者
Christopher Ryan
Principal Investigator
OHSU Knight Cancer Institute