ClinicalTrials.gg
RecruitingNCT06239272Updated Aug 3, 2026

NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)

A Phase 1/2 interventional study of Surgical resection and Proton beam radiation therapy in Adipocytic Neoplasm, Liposarcoma and Atypical Fibroxanthoma, sponsored by St. Jude Children's Research Hospital. Recruiting at 7 sites in United States. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2026-08-03.

Primary conditionLiposarcoma, MyxoidRegistry: LiposarcomaReclassifiedWhy we changed it
Registry
Liposarcoma — the first condition term the registry derived for this study.
ClinicalTrials.gg
Liposarcoma, Myxoid
Why
  1. The study's listed conditions name Liposarcoma, Myxoid, a narrower term within Liposarcoma.
Confidence
High: the new condition is named in the study's own listed conditions. Of 351 hand-checked studies reclassified this way, 68% were exactly right and 84% in the right disease family; the registry's first term was right for 5% (measured 2026-10-21). How we classify →
Wrong?
Tell us the study's main condition →

Sponsored by St. Jude Children's Research Hospital · Phase 1/2, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2024; still recruiting 2 years 7 months later.
Phase
Phase 1/2
Study type
Interventional
Enrollment
139
Allocation
Non-randomized
Ages
Up to 30 Years
Sex
All
01

Study summary

The study participant has been diagnosed with non-rhabdomyosarcoma (NRSTS).

Primary Objectives

Intermediate-Risk

  • To estimate the 3-year event-free survival for intermediate-risk patients treated with ifosfamide, doxorubicin, pazopanib, surgery, and maintenance pazopanib, with or without RT.
  • To characterize the pharmacokinetics of pazopanib and doxorubicin in combination with ifosfamide in intermediate-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and pazopanib and doxorubicin pharmacokinetics.

High-Risk

  • To estimate the maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D) of selinexor in combination with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib in high-risk participants.
  • To characterize the pharmacokinetics of selinexor, pazopanib and doxorubicin in combination with ifosfamide in high-risk participants, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability, and to explore associations between clinical effects and selinexor, pazopanib and doxorubicin pharmacokinetics.

Secondary Objectives

  • To estimate the cumulative incidence of primary site local failure and distant metastasis-free, disease-free, event-free, and overall survival in participants treated on the risk-based treatment strategy defined in this protocol.
  • To define and describe the CTCAE Grade 3 or higher toxicities, and specific grade 1-2 toxicities, in low- and intermediate-risk participants.
  • To study the association between radiation dosimetry in participants receiving radiation therapy and the incidence and type of dosimetric local failure, normal adjacent tissue exposure, and musculoskeletal toxicity.
  • To evaluate the objective response rate (complete and partial response) after 3 cycles for high-risk patients receiving the combination of selinexor with ifosfamide, doxorubicin, pazopanib, and maintenance pazopanib.
  • To assess the relationship between the pharmacogenetic variation in drug-metabolizing enzymes or drug transporters and the pharmacokinetics of selinexor, pazopanib, and doxorubicin in intermediate- or high-risk patients.

Exploratory Objectives

  • To explore the correlation between radiographic response, pathologic response, survival, and toxicity, and tumor molecular characteristics, as assessed through next-generation sequencing (NGS), including whole genome sequencing (WGS), whole exome sequencing (WES), and RNA sequencing (RNAseq).
  • To explore the feasibility of determining DNA mutational signatures and homologous repair deficiency status in primary tumor samples and to explore the correlation between these molecular findings and the radiographic response, survival, and toxicity of patients treated on this protocol.
  • To explore the feasibility of obtaining DNA methylation profiling on pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to assess the correlation with this and pathologic diagnosis, tumor control, and survival outcomes where feasible.
  • To explore the feasibility of obtaining high resolution single-cell RNA sequencing of pretreatment, post-induction chemotherapy, and recurrent (if possible) tumor material, and to characterize the longitudinal changes in tumor heterogeneity and tumor microenvironment.
  • To explore the feasibility of identifying characteristic alterations in non-rhabdomyosarcoma soft tissue sarcoma in cell-free DNA (cfDNA) in blood as a non-invasive method of detecting and tracking changes during therapy, and to assess the correlation of cfDNA and mutations in tumor samples.
  • To describe cardiovascular and musculoskeletal health, cardiopulmonary fitness among children and young adults with NRSTS treated on this protocol.
  • To investigate the potential prognostic value of serum cardiac biomarkers (high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro B-type natriuretic peptide (NT-Pro-BNP), serial electrocardiograms (EKGs), and serial echocardiograms in patients receiving ifosfamide, doxorubicin, and pazopanib, with or without selinexor.
  • To define the rates of near-complete pathologic response (>90% necrosis) and change in FDG PET maximum standard uptake value (SUVmax) from baseline to week 13 in intermediate risk patients with initially unresectable tumors treated with induction pazopanib, ifosfamide, and doxorubicin, and to correlate this change with tumor control and survival outcomes.
  • To determine the number of high-risk patients initially judged unresectable at diagnosis that are able to undergo primary tumor resection after treatment with ifosfamide, doxorubicin, selinexor, and pazopanib.
  • To identify the frequency with which assessment of volumes of interest (VOIs) of target lesions would alter RECIST response assessment compared with standard linear measurements.
Read the detailed description

For the intermediate-risk group, a two-sided one-sample log-rank test will be used to detect an improvement in 3-year EFS from 72% to 86% (power 87% with type I error rate of 5%). With this design, 53 evaluable patients in total will be required. Non-binding interim futility rules will be employed for the combination of subsets of A, B, C at week 10 and a separate rule for subset B at year 2 in terms of local failure rate.

02

Conditions studied

  • Adipocytic Neoplasm
  • Liposarcoma
  • Atypical Fibroxanthoma
  • Angiomatoid Fibrous Histiocytoma
  • Fibrosarcoma NOS
  • Myxofibrosarcoma
  • Angiosarcoma
  • Osteosarcoma, Extraskeletal
  • Dedifferentiated Liposarcoma
  • Myxoid Liposarcoma
  • Pleomorphic Liposarcoma
  • Myxoid Pleomorphic Liposarcoma
  • Low Grade Fibromyxoid Sarcoma
  • Sclerosing Epithelioid Fibrosarcoma
  • Malignant Tenosynovial Giant Cell Tumor of Soft Tissue
  • Epithelioid Hemangioendothelioma
  • Glomus Tumor
  • Inflammatory Leiomyosarcoma
  • Leiomyosarcoma
  • Ossifying Fibromyxoid Tumor, Malignant
  • Myoepithelioma
  • Synovial Sarcoma
  • Epithelioid Sarcoma
  • Perineurioma, Malignant
  • Clear Cell Sarcoma
  • Extraskeletal Myxoid Chondrosarcoma
  • Granular Cell Tumor, Malignant
  • Melanotic Malignant Nerve Sheath Tumor
  • Malignant Peripheral Nerve Sheath Tumor
  • Perivascular Epithelioid Tumor, Malignant
  • Intimal Sarcoma
  • Myoepithelial Carcinoma
  • Undifferentiated Sarcoma
  • Pleomorphic Sarcoma, Undifferentiated
  • Round Cell Sarcoma, Undifferentiated
  • NTRK-Rearranged Spindle Cell Neoplasm
  • Phosphaturic Mesenchymal Tumor, Malignant
  • Round Cell Sarcoma
  • Well Differentiated Liposarcoma
  • Giant Cell Tumor of Soft Parts NOS
  • Low Grade Myofibroblastic Sarcoma
  • Dermatofibrosarcoma Protuberans, Fibrosarcomatous

Keywords

  • Proton therapy
03

In context

Liposarcoma, Myxoid Reclassified

40 studies on the registry are indexed under Liposarcoma, Myxoid; 12 are open to participants now.

This study's planned enrollment of 139 is above the median of 30 across 36 interventional studies indexed under Liposarcoma, Myxoid.

Browse Liposarcoma, Myxoid studies →

Lead sponsor

St. Jude Children's Research Hospital is the lead sponsor of 440 studies on the registry; 102 are open to participants now.

Of its 61 completed or terminated interventional studies of FDA-regulated products, 37 (61%) have results posted.

Compared within Liposarcoma, Myxoid, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Liposarcoma. The counts are of registry records indexed under each term, refreshed daily. How we classify →

04

Who can participate

Ages eligible
Up to 30 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

Inclusion Criteria - All Patients

  • Patients must be 1-30 years at the time of the that established the diagnosis of NRSTS.
  • Surgical Resection: Patients who had an upfront resection prior to enrollment will be eligible if they are able to begin therapy within 28 days of resection assuming other eligibility criteria are met. Delayed resection is preferred for all patients with intermediate and high-risk disease.
  • Lansky performance status score ≥ 60 for patients ≤ 16 years of age. performance status score ≥ 60 for patients >16 years of age. Note patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.

Diagnosis

  • Patients with CIC-DUX 4 rearranged sarcomas will be enrolled on the high-risk stratum only, regardless of presence of , size, or resection status.

Patient has low-risk disease if the patient has a:

  • Low-grade tumor of any size where R0 or R1 surgical margins are anticipated or achieved.
  • High-grade tumors that are \< 5 cm where R0 or R1 resection margins are anticipated or achieved.

Patient must have adequate organ function in the organs that will be within the radiotherapy field.

Adequate renal function defined as:

  • or radioisotope > 70 mL/min/1.73 m2, or
  • A normal serum creatinine based on age/gender as follows

Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 > 16 years 1.5 1.4

Adequate liver function defined as:

  • Total \< 1.5 x (ULN) for age
  • (AST) or SGPT (ALT) \< 2.5 x ULN for age

Adequate cardiac function defined as:

  • of > 55% by echocardiogram or cardiac MRI
  • \< 480 msec

Adequate pulmonary function defined as:

  • No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination.

Inclusion Criteria - Intermediate and High Risk Participants

Patient has intermediate-risk if the patient has a:

  • Low-grade non-metastatic initially unresectable disease at study enrollment where delayed resection is planned.
  • High-grade \< 5 cm non-metastatic initially unresectable disease at study enrollment where delayed resection is planned. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is planned are eligible for this arm.
  • High-grade tumor > 5 cm that is potentially resectable.

Patient high-risk if the patient has:

  • Metastatic disease at presentation
  • Unresectable disease at study enrollment where delayed resection is not anticipated. Of note, patients enrolled on the low-risk arm who were unable to achieve gross total resection where delayed re-resection is not-planned are eligible for this arm.
  • CIC-DUX4 rearranged sarcoma

Organ Function

Adequate bone marrow function defined as:

  • > 1000/µL
  • count > 100,000/µL
  • > 8 g/dL for patients \< 16 years of age
  • Hemoglobin > 9 g/dL for patients > 16 years of age

Note: No transfusions are permitted 7 days prior to laboratory studies to determine eligibility.

Adequate renal function defined as:

  • Creatinine clearance or radioisotope GFR > 70 mL/min/1.73 m2, or
  • A normal serum creatinine based on age/gender as follows

Age Maximum Serum Creatinine (mg/dL) Male Female 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1 1 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 > 16 years 1.5 1.4

Adequate liver function defined as:

  • Total bilirubin \< 1.5 x upper limit of normal (ULN) for age
  • SGOT (AST) or SGPT (ALT) \< 2.5 x ULN for age

Adequate cardiac function defined as:

  • Ejection fraction of > 55% by echocardiogram or cardiac MRI
  • QTc \< 480 msec

Adequate pulmonary function defined as:

  • No evidence of dyspnea at rest, no exercise intolerance, and a resting pulse oximetry reading > 94% on room air if there is clinical indication for determination.

Anticoagulation

Patients on low molecular weight heparin, warfarin (with a stable ), or direct oral anticoagulants (DOAC) who have been on a stable dose of are eligible. Patients being treated for a pulmonary embolism or deep venous thrombosis (DVT) must have been treated for a minimum of 6 weeks prior to starting therapy treatment.

Patient must have a life expectancy of at least 3 months with appropriate therapy.

Exclusion Criteria:

  • Patients with known primary CNS sarcoma or are not eligible. Note: Brain imaging is not an eligibility requirement. Tumors with intracranial extension will be allowed.
  • Patients with the following histologic diagnosis are not eligible: intermediate locally aggressive tumors as defined by WHO, malignant rhabdoid tumor, alveolar soft part sarcoma, infantile fibrosarcoma, unresectable/metastatic dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor, desmoid fibromatosis, rhabdomyosarcoma, desmoplastic small round cell tumor, BCOR-CCNB3 fusion positive sarcoma.
  • Bleeding diathesis: Patients with evidence of active bleeding or bleeding diathesis will be excluded (Note: Patients aged > 17 years with excess of 2.5 mL of hemoptysis are not eligible).
  • Uncontrolled hypertension: Patients with uncontrolled hypertension ( v5 Grade ≥ 2) are ineligible. Hypertension must be well controlled on stable doses of medication for at least two weeks.

Prior Therapy

  • Patients must have had no prior systemic therapy for the treatment of the NRSTS
  • Patients must have had no prior anthracycline or ifosfamide chemotherapy
  • Patients must have had no prior use of pazopanib or similar multi-targeted TKI.

Patients must have had no prior radiotherapy to tumor-involved sites.

Note: Patients previously treated for a non-NRSTS cancer are eligible provided they meet the prior therapy requirements. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded.

  • Substrates WITH Narrow Therapeutic Indices: Patients chronically receiving medications known to be metabolized by CYP3A4 and with narrow therapeutic indices within 7 days prior to study enrollment, including but not limited to pimozide, aripiprazole, triazolam, ergotamine and halofantrine are not eligible. Note: the use of fentanyl is permitted.
  • CYP3A4 Inhibitors: Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin, many NNRTIs, diltiazem, verapamil, and grapefruit juice are not eligible.
  • CYP3A4 Inducers: Patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort are not eligible (with the exception of ).
  • Certain medications that are associated with a risk for QTc prolongation and/or Torsade's de Pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible.
  • Subjects with any condition that may impair the ability to absorb oral medications/ product including:

    • prior surgical procedures affecting absorption including, but not limited to major resection of stomach or small bowel
    • active peptic ulcer disease
    • malabsorption syndrome

3.4.12 Thyroid Replacement Therapy: Patients who require thyroid replacement therapy are not eligible if they have not been receiving a stable replacement dose for at least 4 weeks prior to study enrollment.

3.4.13 Subjects with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

  • active peptic ulcer disease
  • known intraluminal metastatic lesions
  • inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or other gastrointestinal conditions which increase the risk of perforation
  • history of abdominal fistula, gastrointestinal perforation or intra- abdominal abscess within 28 days prior to beginning study treatment.

3.4.14 Pulmonary embolism or DVT. Patients must not have experienced:

  • An untreated pulmonary embolism or DVT in last 6 months or
  • treated pulmonary embolism or DVT which has been treated with therapeutic anticoagulation for less than 6 weeks
  • arterial thrombosis in last 12 months

History of serious or non-healing wound, ulcer, or bone fracture.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pazopanib. In addition, these subjects are at increased risk of lethal infections when treated with marrow-suppressive therapy.

Patients who are receiving any other investigational agent(s).

Pregnancy and Breast Feeding

  • Pregnancy and Breast Feeding Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies.
  • Lactating females are not eligible unless they have agreed not to breastfeed their infants during treatment and for a period of 1 month following completion of treatment.
  • Female patients of are not eligible unless a negative pregnancy test result has been obtained.
  • Unwillingness to use an effective method for the duration of their study participation and for at least 1 month after treatment is completed if sexually active with .
Terms in these criteria, in plain language(24)

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.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Karnofsky performance status (KPS)

A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.

Studies often ask for 60 or 70 and above. Your doctor gives the score.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

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.

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.

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.

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.

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.

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.

QT and QTc

On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.

The study may name a correction formula and a limit in milliseconds, often around 450–480.

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.

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.

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).

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

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.

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.

05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Factorial assignment
Masking
None (open label)
Enrollment
139 participants (estimated)

Study arms

  • Experimental
    Low-Risk Subset A

    Participants with low grade tumors of any size, or high-grade tumors \< 5 cm that have been (or are expected to be) completely removed by surgery. When the pathologist reviews the tumor specimen, the tissue around the tumor (margins) must be negative for cancer cells, meaning all of the cancer has been removed. These participants will have surgery to remove the tumor, followed by close observation. There will no further therapy after surgery, just monitoring for tumor recurrence and any side effects from surgery.

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy

  • Experimental
    Low-Risk Subset B

    Participants with high-grade tumors that are \< 5 cm with positive margins. This means that the pathologist finds cancer cells at the edge of the tissue, suggesting that all of the cancer has not been removed. These participants will have surgery followed by radiation therapy for about 5-6 weeks.

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy

  • Experimental
    Intermediate-Risk Subset A (participants with low grade tumors):

    * If your tumor is completely removed at surgery \[meaning the tissue around the tumor (margins) is negative for tumor cells\], you will receive no further therapy and you will be closely observed for any signs of tumor recurrence. * If your tumor cannot be completely removed at surgery \[meaning the tissue around the tumor (margins) is positive for tumor cells\] and the tumor is low-grade, you will get consolidation therapy with additional chemotherapy and radiation therapy, followed by 6 months of maintenance therapy with pazopanib.

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy · Drug: Pazopanib · Drug: Ifosfamide · Drug: Doxorubicin

  • Experimental
    Intermediate-Risk Subset B (participants with high-grade tumors between 5 and 10 cm in size

    * If your tumor is completely removed at surgery \[meaning the tissue around the tumor (margins) is negative for tumor cells\] you will continue with consolidation chemotherapy with additional chemotherapy without radiation therapy, followed by 6 months of maintenance therapy with pazopanib. * If your tumor cannot be completely removed at surgery \[meaning the tissue around the tumor (margins) is positive for tumor cells\], you will get consolidation therapy with additional chemotherapy and radiation therapy, followed by 6 months of maintenance therapy with pazopanib.

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy · Drug: Pazopanib · Drug: Ifosfamide · Drug: Doxorubicin

  • Experimental
    Intermediate-Risk Subset C (participants with high-grade tumors > 10 cm):

    * After 3 cycles of induction chemotherapy, your doctor may decide to give an additional 4th cycle if he/she thinks it would be beneficial before surgery. * You will get consolidation therapy with additional chemotherapy and radiation therapy, followed by 6 months of maintenance therapy with pazopanib. The dose of radiation that you receive will be higher if your tumor cannot be completely removed at surgery (positive margins).

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy · Drug: Pazopanib · Drug: Ifosfamide · Drug: Doxorubicin

  • Experimental
    High-Risk - 2 groups

    * If you have a low-grade tumor that has spread to other parts of the body AND the surgeon was able to completely remove all tumors from all parts of your body, you will have no further therapy after surgery. You will be closely followed to monitor you for any signs of tumor recurrence. * If you have a high-grade tumor OR a tumor that cannot be completely removed by surgery OR you have the CIC-DUX4 mutation, you will get consolidation chemotherapy and radiation therapy, followed by 6 months of maintenance therapy with pazopanib.

    Procedure: Surgical resection · Radiation: Proton beam radiation therapy · Drug: Pazopanib · Drug: Ifosfamide · Drug: Doxorubicin · Drug: Selinexor

Interventions

  • ProcedureSurgical resection

    Low, Intermediate and High-risk Surgery to remove tumor (standard of care)

  • RadiationProton beam radiation therapy

    Low, Intermediate and High-risk Radiation therapy is considered standard of care for patients with NRSTS who have positive tumor margins. However, the dose that will be given in this study is higher than what is usually given, therefore, the dose of radiation in this study is research. Radiation will start about 3 to 6 weeks after your surgery, depending on how quickly you recover from surgery. Radiation will be given daily (Monday through Friday) for about 5 to 6 weeks.

  • Intermediate and High-risk By mouth, either by tablet or a liquid suspension, 7 doses, days 1 to 7

    Also known as: VOTRIENT®

  • Intermediate and High-risk Ifosfamide is a structural analogue of cyclophosphamide. Into the vein (IV) over about 3 hours, 3 doses, days 1, 2, and 3

    Also known as: Ifex

  • Intermediate and High-risk An anthracycline antibiotic isolated from cultures of Streptomyces peucetius. Intermediate, High-risk Into the vein (IV) over about 1 hour, 2 doses, days 1 and 2

    Also known as: Adriamycin®, Rubex®

  • High-risk Dosage and route of administration: Selinexor tablets for oral administration should be taken at approximately the same time each day without regards to meals. Selinexor is a selective inhibitor of nuclear export (SINE). Selinexor specifically blocks XPO1-mediated nuclear export by forming a slowly reversible covalent bond with the nuclear export protein XPO1 By mouth, either by tablet or a liquid suspension, 1 dose and day 3

    Also known as: XPOVIO®

06

What researchers measure

Primary outcomes

  1. Event-free survival (EFS)

    We will estimate the 3-year event-free survival for intermediate-risk patients, which is the estimated probability of a patient not having any events within the 3-year follow-up. The events are defined as including local failure, regional failure, distant failure, a subsequent malignant neoplasm, or death, whichever occurred first.

    Time frame: 9 years (6 years of accrual and 3 year follow-up after enrollment of last patient

  2. Maximum tolerated dose (MTD) and/or the recommended phase 2 dosage (RP2D)

    MTD is defined in the study as the highest treatment dose that would deliver desirable treatment effects without resulting in a target toxicity rate greater than 0.3. We will employ the Bayesian optimal interval (BOIN) design to find the MTD in high-risk participants.

    Time frame: 4 years]

07

Study locations

7 of 7 sites recruiting
  • Children's Healthcare of Atlanta
    Atlanta, Georgia 30329, United States
    Recruiting
    • Kathryn Sutton, MD · Contact
    • Kathryn Sutton, MD · Principal investigator
  • Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
    Recruiting
    • Jennifer Reicheck, MD · Contact
    • Jennifer Reicheck, MD · Principal investigator
  • Our Lady of the Lake Children's Hospital
    Baton Rouge, Louisiana 70809, United States
    Recruiting
    • Jeffrey Deyo, MD · Contact
    • Jeffrey Deyo, MD · Principal investigator
  • Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Recruiting
    • Natalie Collins, MD · Contact
    • Natalie Collins, MD · Principal investigator
  • Washington University Medical Center
    St Louis, Missouri 63110, United States
    Recruiting
    • Amy Armstrong, MD · Contact
    • Amy Armstrong, MD · Principal investigator
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
    Recruiting
    • Brian Turpin, MD · Contact
    • Brian Turpin, MD · Principal investigator
  • St. Jude Children's Research Hospital
    Memphis, Tennessee 38105, United States
    Recruiting
    • Jessica Gartrell, MD · Contactreferralinfo@stjude.org · 888-226-4343
    • Jessica Gartrell, MD · Principal investigator
08

References and documents

Individual participant data

Plan to share: Yes — Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.

Supporting information: Statistical analysis plan, Informed consent form, Clinical study report

Time frame: Data will be made available at the time of article publication.

Access criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06239272
Responsible party
Sponsor
First posted
Feb 2, 2024
Start date
Mar 27, 2024
Primary completion
Jun 2034 (estimated)
Completion
Jun 2037 (estimated)
Last update
Aug 3, 2026

Study contacts

Jessica Gartrell, MD
Contact
referralinfo@stjude.org
888-226-4343
Jessica Gartrell, MD
principal investigator · St. Jude Children's Research Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Pazopanib · Selinexor

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