A Phase 2 interventional study of High-dose Methotrexate in Osteosarcoma in Children and Osteosarcoma in Adolescents and Young Adults, sponsored by Wake Forest University Health Sciences. Recruiting at 9 sites in United States. Open to participants aged 7 Years to 22 Years. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Wake Forest University Health Sciences · Phase 2, Interventional, and Supportive care
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:
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.
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.
488 studies on the registry are indexed under Osteosarcoma; 124 are open to participants now.
This study's planned enrollment of 46 is above the median of 40 across 354 interventional studies indexed under Osteosarcoma.
Browse Osteosarcoma studies →Wake Forest University Health Sciences is the lead sponsor of 1,351 studies on the registry; 201 are open to participants now.
Of its 332 completed or terminated interventional studies of FDA-regulated products, 251 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Pre-Enrollment Criteria:
Inclusion Criteria:
Participants receiving or planning to receive induction/ 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 must meet minimum organ function requirements to receive HD-MTX:
Adequate cardiac function, defined as a (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.
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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: High-dose Methotrexate
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.
Incidence of Dose Limiting Toxicity (DLT)
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
Time frame: Within 7-days post-discharge of methotrexate visit
Length of Stay (LOS)
Length of hospital stay measured in hours from time of admission to time of discharge for each HD-MTX inpatient cycle
Time frame: 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
Total estimated cost associated with each HD-MTX inpatient cycle, based on hospital billing charges and nights of stay
Time frame: Approximately 30 weeks per participant from first week of treatment
Plan to share: No
No publications or documents are linked to this record.
Started Oct 2026 (actual). Primary completion is estimated for Dec 2028, 26 months after the start.
Of 72 non-industry phase 2 interventional studies under Osteosarcoma, half reached primary completion within 66 months of starting (the median), counting those still running; a quarter within 41 and three quarters within 94. This study's planned 26 months is below that.
Counting every sponsor, half of 76 studies reached it within 65 months; a quarter within 40 and three quarters within 94.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Methotrexate
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