ClinicalTrials.gg
Sign In
RecruitingNCT05828069Updated Oct 30, 2026

A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis

A Phase 2 interventional study of Biospecimen Collection and Bone Marrow Aspiration in Recurrent Langerhans Cell Histiocytosis and Refractory Langerhans Cell Histiocytosis, sponsored by National Cancer Institute (NCI). Recruiting at 123 sites in 3 countries. Open to participants aged 180 Days to 22 Years. Per ClinicalTrials.gov, last updated 2026-10-30.

Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Mar 2024; still recruiting 2 years 7 months later.
Updated Oct 30, 2026Site recruiting status changed4 sites added+1 moreGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
48
Allocation
Not applicable
Ages
180 Days to 22 Years
Sex
All
01

Study summary

This phase II trial tests the safety, side effects, best dose and activity of tovorafenib (DAY101) in treating patients with Langerhans cell histiocytosis that is growing, spreading, or getting worse (progressive), has come back (relapsed) after previous treatment, or does not respond to therapy (refractory). Langerhans cell histiocytosis is a type of disease that occurs when the body makes too many immature Langerhans cells (a type of white blood cell). When these cells build up, they can form tumors in certain tissues and organs including bones, skin, lungs and pituitary gland and can damage them. This tumor is more common in children and young adults. DAY101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Using DAY101 may be effective in treating patients with relapsed or refractory Langerhans cell histiocytosis.

Read the detailed description

PRIMARY OBJECTIVE:

I. To determine overall response rate (ORR) for children and young adults with relapsed or refractory BRAFV600E positive (cohort 1) and BRAFV600E negative (cohort 2) Langerhans cell histiocytosis (LCH) treated with tovorafenib (DAY101) after 2 cycles and must be maintained 4 weeks later.

SECONDARY OBJECTIVES:

I. To determine nature and severity of adverse events in patients treated with tovorafenib (DAY101) for relapsed or refractory LCH.

II. To describe event-free survival (EFS) at 1 year in children and young adults with relapsed and refractory LCH treated with tovorafenib (DAY 101) for up to 1 year.

III. To determine durability of response in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) following cessation of therapy in patients with complete response (CR) at 1 year.

IV. To describe progression-free (and relapse-free) survival (PFS) and overall survival (OS) in children and young adults with relapsed or refractory LCH treated with tovorafenib (DAY101) for up to 1 year.

EXPLORATORY OBJECTIVES:

I. To determine potential role of pathogenic tumor mutation in response to tovorafenib (DAY101), and to evaluate changes in bone marrow and peripheral blood cell populations carrying pathogenic mutations in response to tovorafenib (DAY101) therapy.

Ia. To define somatic mutations in LCH lesion biopsies; Ib. To determine impact of tovorafenib (DAY101) on bone marrow and blood BRAFV600E+ mononuclear cells; Ic. To determine impact of tovorafenib (DAY101) on cerebral spinal fluid and disease response; Id. To determine the performance of standardized immunohistochemical analysis of LCH lesion biopsies.

II. To compare performance of LCH-specific response criteria to Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

III. To describe the pharmacokinetics of tovorafenib (DAY101) when administered to pediatric and young adult patients with relapse or refractory LCH.

OUTLINE: This is a dose escalation study of tovorafenib followed by a phase II trial.

Patients receive tovorafenib orally (PO) once weekly (QW) on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo multi-gated acquisition (MUGA) or echocardiography (ECHO) scans, and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) or computed tomography (CT) throughout the trial, and collection of blood and urine samples on study. Patients with suspicion of bone marrow and/or central nervous system involvement will also undergo bone marrow biopsy and aspiration and lumbar puncture on study and during follow up.

After completion of study treatment, patients are followed up at 28 days, months 3, 6, 9, and 12, and then at 2 years post cycle 12.

02

Conditions studied

  • Recurrent Langerhans Cell Histiocytosis
  • Refractory Langerhans Cell Histiocytosis
03

In context

Histiocytosis, Langerhans-Cell

81 studies on the registry are indexed under Histiocytosis, Langerhans-Cell; 23 are open to participants now.

This study's planned enrollment of 48 is above the median of 24 across 64 interventional studies indexed under Histiocytosis, Langerhans-Cell.

Browse Histiocytosis, Langerhans-Cell studies →

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
180 Days to 22 Years
Sexes eligible
All
Accepts healthy volunteers
No

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.

Inclusion criteria

  • 180 days- \< 22 years (at time of study enrollment)
  • Patient must have a body surface area of ≥ 0.3 m\^2

  • Patients with progressive, , or recurrent LCH with at study entry

    • Patients must have had histologic verification of LCH (from either original diagnosis or relapse/progression) at the time of study entry

      • Tissue confirmation of relapse is recommended but not required.
      • Pathology report must be submitted for central confirmation of diagnosis within 7 days of enrollment.
      • Formalin-fixed paraffin-embedded (FFPE) blocks or unstained slides (initial diagnosis and/or subsequent ) will be required for retrospective central confirmation of diagnosis and molecular studies
      • Patients with mixed histiocytic disorders (e.g. LCH with juvenile xanthogranuloma) may be included
    • Patients must have measurable disease
    • Patients must have progressive or refractory disease or experience relapse after at least one previous systemic treatment strategy
    • Pathogenic somatic mutation detected in genes encoding tyrosine kinase receptors (CSFR1, ERBB3 or ALK), RAS or RAF (may be from original or subsequent biopsy or peripheral blood/bone marrow aspirate). Clinical mutation reports may include quantitative polymerase chain reaction (PCR) (e.g. BRAFV600E) and/or Sanger or next generation sequencing. Immunohistochemistry (e.g. VE1 antibody for BRAFV600E) alone is not sufficient
  • Participant must be able to take an enteral dose and formulation of medication. Study medication is only available as an oral suspension or tablet, which may be taken by mouth or other enteral route such as nasogastric, jejunostomy, or gastric tube
  • >= 50% for patients > 16 years of age and Lansky >= 50% for patients =\< 16 years of age
  • Patients must have a performance status corresponding to (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =\< 16 years of age
  • Myelosuppressive chemotherapy: Patients must not have received within 14 days of entry onto this study
  • agent or any other anticancer therapy not defined above: Patients must not have received any investigational agent or any other anticancer therapy (including MAPK pathway inhibitor) for at least 14 days prior to planned start of tovorafenib (DAY101)
  • Radiation therapy (RT): Patient must not have received RT within 2 weeks after the last dose fraction of RT
  • Patients must have fully recovered from any prior surgery
  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, targeted inhibitor, and/or radiotherapy with toxicities reduced to grade 1 or less ( [CTCAE] version 5.0)
  • : =\< 0.5 mg/kg/day of prednisone equivalent (maximum 20 mg/day) averaged during the month prior to study enrollment is permissible
  • Strong inducers or inhibitors of CYP2C8 are prohibited for 14 days before the first dose of tovorafenib (DAY101) and from planned administration for the duration of study participation
  • Medications that are breast cancer resistant protein (BCRP) substrates that have a narrow therapeutic index are prohibited for 14 days before the first dose of tovorafenib (DAY101) and for the duration of study participation
  • Peripheral (ANC) >= 750/uL unless secondary to bone marrow involvement, in such cases bone marrow involvement must be documented (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
  • count >= 75,000/uL (unsupported/without transfusion within the past 7 days) (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
  • Patients with marrow disease must have platelet count of >= 75,000/uL (transfusion support allowed) and must not be refractory to platelet transfusions. Bone marrow involvement must be documented
  • >= 8 g/dL (unsupported/without transfusion within the past 7 days). Patients with marrow disease must have hemoglobin >= 8 g/dL (transfusion support allowed). Bone marrow involvement must be documented
  • Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta [registered trademark]) or 7 days for short-acting growth factor

  • A serum creatinine based on age/sex as follows (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)

    • Age: 6 months to \< 1 year; Maximum Serum Creatinine (mg/dL):= 0.5 mg/dl (male and female)
    • Age: 1 to \< 2 years; Maximum Serum Creatinine (mg/dL): = 0.6 mg/dl (male and female)
    • Age: 2 to \< 6 years; Maximum Serum Creatinine (mg/dL): = 0.8 mg/dl (male and female)
    • Age: 6 to \< 10 years; Maximum Serum Creatinine (mg/dL): = 1.0 mg/dl (male and female)
    • Age: 10 to \< 13 years; Maximum Serum Creatinine (mg/dL): = 1.2 mg/dl (male and female)
    • Age: 13 to \< 16 years; Maximum Serum Creatinine (mg/dL): = 1.5 mg/dl (male) and 1.4 mg/dl (female)
    • Age: >= 16 years; Maximum Serum Creatinine (mg/dL): = 1.7 mg/dl (male) and 1.4 mg/dl (female)
    • OR- a 24 hour urine >= 50 mL/min/1.73 m\^2
    • OR- a (GFR) >= 50 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
    • Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
  • (sum of conjugated + unconjugated) =\< 1.5 x (ULN) for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
  • (ALT) =\< 3 x ULN for age (must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
  • Serum albumin >= 2 g/dl must be performed within 7 days prior to enrollment, must be repeated prior to the start of protocol therapy if > 7 days have elapsed from their most recent prior assessment)
  • For patients with liver disease caused by their histiocytic disorder (as evaluated on radiographic imaging or biopsy): patients may be enrolled with abnormal bilirubin, aspartate aminotransferase (AST), ALT and albumin with documentation of histiocytic liver disease
  • Fractional shortening (FS) of >= 25% or of >= 50%, as determined by echocardiography or multigated acquisition scan (MUGA) within 28 days prior to study enrollment. Depending on institutional standard, either FS or left ventricular ejection fraction (LVEF) is adequate for enrollment if only one value is measured; if both values are measured, then both values must meet criteria above (must be obtained within 28 days prior to enrollment and start of protocol therapy) (repeat if necessary)
  • No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination; unless it is due to underlying pulmonary LCH

  • Central Nervous System Function Defined As:

    • Patients with seizure disorder may be enrolled if well controlled
    • Central nervous system (CNS) toxicity =\< Grade 2
  • (HIV) infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial unless antiretroviral therapy interacts with the metabolism of tovorafenib (DAY101) and cannot safely be changed to antivirals that do not interact with study medication
  • All patients and/or their parent(s) or legal guardians must sign a written
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Exclusion criteria

Exclusion Criteria:

  • LCH arising along with other hematologic (e.g. mixed LCH with acute lymphoblastic leukemia) or any history of non-histiocytic malignancy

  • Disease scenarios as below will be excluded

    • Skin-limited disease
    • Gastrointestinal (GI) tract involvement only (those that have disease that can be determined by endoscopic only)
    • LCH-associated neurodegeneration (LCH-ND) without parenchymal lesions or other systemic lesions
  • Patients with activating mutations in MAP2K1 are not eligible for this study due to drug target specificity. Mutation status will be submitted to study team within 7 days of enrollment
  • nausea and vomiting, malabsorption, or external biliary shunt that would preclude adequate absorption of tovorafenib (DAY101)
  • Uncontrolled systemic bacterial, viral, or fungal infection
  • Major surgical procedure or significant traumatic injury within 14 days prior to study enrollment, or anticipation of need for major surgical procedure during the course of the study. Placement of a vascular access device or minor surgery is permitted within fourteen (14) days of study enrollment (provided that the wound has healed)
  • History of significant bowel resection that would preclude adequate absorption or other significant malabsorptive disease
  • Ophthalmologic considerations: Patients with known significant ophthalmologic conditions or known risk factors for retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible
  • History of solid organ or hematopoietic bone marrow transplantation
  • active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis/pulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged > 440 ms based on triplicate (ECG) average
  • History of Grade >= 2 CNS hemorrhage or history of any CNS hemorrhage within 28 days of study entry
  • History of any drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS) or who are allergic to tovorafenib (DAY101) or any of its components
  • version (V.) 5.0 Grade 3 symptomatic creatinine kinase (CPK) elevation (> 5 x )
  • Female patients who are pregnant are ineligible. A pregnancy test is required for female patients of
  • Lactating females who plan to breastfeed their infants are ineligible
  • Sexually active patients of who have not agreed to use an effective method for the duration of their study participation are ineligible. Women of childbearing potential must use non-hormonal contraception during tovorafenib treatment and for at least 28 days after the last dose. Men should use effective contraception and must not father a child while taking tovorafenib and for 14 days after the last dose
Terms in these criteria, in plain language(26)

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.

Relapsed and refractory

Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

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.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

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.

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.

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.

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).

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.

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.

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.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

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.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

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.

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.

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
48 participants (estimated)

Study arms

  • Experimental
    Treatment (tovorafenib)

    Patients receive tovorafenib PO QW on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO scans, and FDG-PET or CT throughout the trial, and collection of blood and urine samples on study. Patients with suspicion of bone marrow and/or central nervous system involvement will also undergo bone marrow biopsy and aspiration and lumbar puncture on study and during follow up.

    Procedure: Biospecimen Collection · Procedure: Bone Marrow Aspiration · Procedure: Bone Marrow Biopsy · Procedure: Computed Tomography · Procedure: Echocardiography Test · Procedure: FDG-Positron Emission Tomography and Computed Tomography Scan · Procedure: Lumbar Puncture · Procedure: Multigated Acquisition Scan · Drug: Tovorafenib

Interventions

  • ProcedureBiospecimen Collection

    Undergo collection of blood and urine samples

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • ProcedureBone Marrow Aspiration

    Undergo bone marrow aspiration

  • ProcedureBone Marrow Biopsy

    Undergo bone marrow biopsy

    Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

  • ProcedureComputed Tomography

    Undergo CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

  • ProcedureEchocardiography Test

    Undergo ECHO

    Also known as: EC, Echocardiography

  • ProcedureFDG-Positron Emission Tomography and Computed Tomography Scan

    Undergo FDG-PET imaging

    Also known as: FDG PET/CT

  • ProcedureLumbar Puncture

    Undergo lumbar puncture

    Also known as: LP, Spinal Tap

  • ProcedureMultigated Acquisition Scan

    Undergo MUGA

    Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

  • DrugTovorafenib

    Given PO

    Also known as: BIIB 024, BIIB-024, BIIB024, DAY 101, DAY-101, DAY101, MLN 2480, MLN-2480, MLN2480, Ojemda, pan-RAF Kinase Inhibitor DAY101, TAK 580, TAK-580, TAK580

06

What researchers measure

Primary outcomes

  1. Frequency of dose limiting toxicity (dose finding phase)

    Will be analyzed descriptively.

    Time frame: Up to 28 days

  2. Overall response rate (phase II)

    Will be assessed using minimax Simon's two-stage designs in each of the BRAFV600E and non-BRAFV600E cohorts separately. The two arms will not be directly compared. The 95% confidence interval for the overall response rate will be adjusted for the two-stage design.

    Time frame: After 2 cycles of therapy (each cycle is 28 days)

Secondary outcomes

  1. Event free survival rate

    Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals. Events are defined as relapse/progression, second malignant neoplasm, or death.

    Time frame: At 1 and 2 years

  2. Progression free survival rate

    Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated by two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals.

    Time frame: Up to 2 years

  3. Duration of response rate

    Response is based on modified Response Evaluation Criteria for Solid Tumors (RECIST)/Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) consistent with other recent pediatric Langerhans Cell Histiocytosis trials (NCT02670707 and NCT04079179) and adult histiocytosis trials with MAPK inhibitors. Comparison of response assessed via RECIST versus (vs.) PERCIST will be analyzed by displaying two-way tables of the responses with no formal statistical testing.

    Time frame: After 12 months of therapy. From the scan confirming the complete response or partial response (whichever is recorded first), until the first occurrence of recurrent or progressive disease or death (event) or last known status on trial

  4. Overall survival rate

    Will be estimated by the Kaplan-Meier method beginning at study enrollment. Will be evaluated two years after enrollment of the last patient on the trial and estimates at specific timepoints will be presented along with log-log transformed 95% confidence intervals.

    Time frame: Up to 2 years

Other outcomes

  1. Percent peripheral blood mononuclear cells with mutated allele

    Will be analyzed descriptively using logistic regression with complete response/progressive response vs. stable disease/progressive disease as the response variable.

    Time frame: Up to 2 years

07

Study locations

117 of 123 sites recruiting

Showing the first 100 of 123 sites across 3 countries. Choose a country and city above to see the rest.

08

References and documents

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Data sharing details ↗ · grants.nih.gov

No publications or documents are linked to this record.

09

Timeline

15 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Started Mar 2024 (actual). Primary completion is estimated for Sep 2028, 54 months after the start.

Of 32 phase 2 interventional studies under Histiocytosis, Langerhans-Cell, half reached primary completion within 63 months of starting (the median), counting those still running; a quarter within 55 and three quarters within 85. This study's planned 54 months is below that.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 21, 2023
First posted
Apr 25, 2023
StartActual
Mar 28, 2024
Primary completionEst.
Sep 30, 2028
CompletionEst.
Sep 30, 2028
Last update
Oct 30, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Sites
4 sites added, 1 site removed. 7 sites changed recruiting status (6 now recruiting, 1 now suspended)
Show 7 sites
  • Hospital for Sick Children · Toronto, CanadaSuspended→Recruiting
  • Children's Hospital · London, CanadaSuspended→Recruiting
  • University of Miami Miller School of Medicine-Sylvester Cancer Center · Miami, United StatesRecruiting→Suspended
  • Sydney Children's Hospital · Randwick, AustraliaSuspended→Recruiting
  • Queensland Children's Hospital · South Brisbane, AustraliaSuspended→Recruiting
  • Royal Children's Hospital · Parkville, AustraliaSuspended→Recruiting
  • Perth Children's Hospital · Perth, AustraliaSuspended→Recruiting
Show 4 added (2 United States, 1 Australia, 1 Canada)
  • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
  • John Hunter Children's Hospital · Hunter Regional Mail Centre, Australia
  • The Montreal Children's Hospital of the MUHC · Montreal, Canada
  • Morristown Medical Center · Morristown, United States
Show 1 removed
  • West Virginia University Charleston Division · Charleston, United States
across 13 updates, Sep 25, 2026 – Oct 30, 2026
Site contacts
Changed at 17 sites. See the sites
Show 17 sites
  • Memorial Health University Medical Center · Savannah, United StatesContact person changed (no phone or email listed)
  • West Virginia University Charleston Division · Charleston, United StatesContact none listed→C•••@vandaliahealth.org
  • Connecticut Children's Medical Center · Hartford, United StatesContact added •••9981Contact added (no phone or email listed)
  • Mission Hospital · Asheville, United StatesContact added N•••@hcahealthcare.com · •••7055Contact added (no phone or email listed)
  • Nicklaus Children's Hospital · Miami, United StatesContact added •••2778Contact added (no phone or email listed)
  • Nemours Children's Clinic - Pensacola · Pensacola, United StatesContact added h•••@childrensoncologygroup.orgContact added (no phone or email listed)
  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center · Houston, United StatesContact added b•••@bcm.edu · •••1354Contact added (no phone or email listed)
  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation · Las Vegas, United StatesContact person changed (no phone or email listed)
  • Summerlin Hospital Medical Center · Las Vegas, United StatesContact person changed (no phone or email listed)
  • Hospital for Sick Children · Toronto, CanadaContact added a•••@sickkids.ca · •••7654Contact added (no phone or email listed)
  • Scott and White Memorial Hospital · Temple, United StatesContact added •••5407Contact added (no phone or email listed)
  • Children's Hospital · London, CanadaContact added •••8306Contact added (no phone or email listed)
  • University of Miami Miller School of Medicine-Sylvester Cancer Center · Miami, United StatesContact removed •••2647Contact removed (no phone or email listed)
  • Sydney Children's Hospital · Randwick, AustraliaContact added •••1721Contact added (no phone or email listed)
  • Queensland Children's Hospital · South Brisbane, AustraliaContact added •••1111Contact added (no phone or email listed)
  • Royal Children's Hospital · Parkville, AustraliaContact added J•••@rch.org.au · •••5656Contact added (no phone or email listed)
  • Perth Children's Hospital · Perth, AustraliaContact added h•••@childrensoncologygroup.orgContact added (no phone or email listed)
across 12 updates, Sep 25, 2026 – Oct 21, 2026
Show all 15 updates
  1. Oct 30, 2026
    1 site added
    Show site
    • Morristown Medical Center · Morristown, United States
  2. Oct 29, 2026
    1 site added
    Show site
    • The Montreal Children's Hospital of the MUHC · Montreal, Canada
  3. Oct 21, 2026
    1 site added. 6 sites changed recruiting status (5 now recruiting, 1 now suspended)
    Show 6 sites
    • University of Miami Miller School of Medicine-Sylvester Cancer Center · Miami, United StatesRecruiting→Suspended
    • Scott and White Memorial Hospital · Temple, United StatesSuspended→Recruiting
    • Sydney Children's Hospital · Randwick, AustraliaSuspended→Recruiting
    • Queensland Children's Hospital · South Brisbane, AustraliaSuspended→Recruiting
    • Royal Children's Hospital · Parkville, AustraliaSuspended→Recruiting
    • Perth Children's Hospital · Perth, AustraliaSuspended→Recruiting
    Show site
    • John Hunter Children's Hospital · Hunter Regional Mail Centre, Australia
    Site contacts Changed at 6 sites. See the sites
    Show 6 sites
    • University of Miami Miller School of Medicine-Sylvester Cancer Center · Miami, United StatesContact removed •••2647Contact removed (no phone or email listed)
    • Scott and White Memorial Hospital · Temple, United StatesContact added •••5407Contact added (no phone or email listed)
    • Sydney Children's Hospital · Randwick, AustraliaContact added •••1721Contact added (no phone or email listed)
    • Queensland Children's Hospital · South Brisbane, AustraliaContact added •••1111Contact added (no phone or email listed)
    • Royal Children's Hospital · Parkville, AustraliaContact added J•••@rch.org.au · •••5656Contact added (no phone or email listed)
    • Perth Children's Hospital · Perth, AustraliaContact added h•••@childrensoncologygroup.orgContact added (no phone or email listed)
  4. Oct 19, 2026
    2 sites changed recruiting status (1 now suspended, 1 now recruiting)
    Show 2 sites
    • Scott and White Memorial Hospital · Temple, United StatesRecruiting→Suspended
    • Children's Hospital · London, CanadaSuspended→Recruiting
    Site contacts Changed at 2 sites. See the sites
    Show 2 sites
    • Scott and White Memorial Hospital · Temple, United StatesContact removed •••5407Contact removed (no phone or email listed)
    • Children's Hospital · London, CanadaContact added •••8306Contact added (no phone or email listed)
  5. Oct 16, 2026
    3 sites changed recruiting status (3 now recruiting)
    Show 3 sites
    • Nemours Children's Clinic - Pensacola · Pensacola, United StatesSuspended→Recruiting
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center · Houston, United StatesSuspended→Recruiting
    • Hospital for Sick Children · Toronto, CanadaSuspended→Recruiting
    Site contacts Changed at 5 sites. See the sites
    Show 5 sites
    • Nemours Children's Clinic - Pensacola · Pensacola, United StatesContact added h•••@childrensoncologygroup.orgContact added (no phone or email listed)
    • Alliance for Childhood Diseases/Cure 4 the Kids Foundation · Las Vegas, United StatesContact person changed (no phone or email listed)
    • Summerlin Hospital Medical Center · Las Vegas, United StatesContact person changed (no phone or email listed)
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center · Houston, United StatesContact added b•••@bcm.edu · •••1354Contact added (no phone or email listed)
    • Hospital for Sick Children · Toronto, CanadaContact added a•••@sickkids.ca · •••7654Contact added (no phone or email listed)
  6. Oct 15, 2026
    Mission Hospital is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Mission Hospital · Asheville, United StatesContact added N•••@hcahealthcare.com · •••7055Contact added (no phone or email listed)
  7. Oct 14, 2026
    3 sites changed recruiting status (2 now suspended, 1 now recruiting)
    Show 3 sites
    • Nicklaus Children's Hospital · Miami, United StatesSuspended→Recruiting
    • Nemours Children's Clinic - Pensacola · Pensacola, United StatesRecruiting→Suspended
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center · Houston, United StatesRecruiting→Suspended
    Site contacts Changed at 3 sites. See the sites
    Show 3 sites
    • Nicklaus Children's Hospital · Miami, United StatesContact added •••2778Contact added (no phone or email listed)
    • Nemours Children's Clinic - Pensacola · Pensacola, United StatesContact removed h•••@childrensoncologygroup.orgContact removed (no phone or email listed)
    • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center · Houston, United StatesContact removed b•••@bcm.edu · •••1354Contact removed (no phone or email listed)
  8. Oct 13, 2026
    Nicklaus Children's Hospital is now Suspended
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Nicklaus Children's Hospital · Miami, United StatesContact removed •••2778Contact removed (no phone or email listed)
  9. Oct 8, 2026
    Connecticut Children's Medical Center is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Connecticut Children's Medical Center · Hartford, United StatesContact added •••9981Contact added (no phone or email listed)
  10. Oct 6, 2026
    2 sites changed recruiting status (2 now suspended)
    Show 2 sites
    • Connecticut Children's Medical Center · Hartford, United StatesRecruiting→Suspended
    • Mission Hospital · Asheville, United StatesRecruiting→Suspended
    Site contacts Changed at 2 sites. See the sites
    Show 2 sites
    • Connecticut Children's Medical Center · Hartford, United StatesContact removed •••9981Contact removed (no phone or email listed)
    • Mission Hospital · Asheville, United StatesContact removed N•••@hcahealthcare.com · •••7055Contact removed (no phone or email listed)
  11. Oct 2, 2026
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Memorial Health University Medical Center · Savannah, United StatesContact person changed (no phone or email listed)
  12. Oct 1, 2026
    1 site added, 1 site removed
    Show site
    • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
    Show 1 removed
    • West Virginia University Charleston Division · Charleston, United States
  13. Sep 29, 2026
    Site contacts Changed at 1 site. See the sites
    Show the site
    • West Virginia University Charleston Division · Charleston, United StatesContact none listed→C•••@vandaliahealth.org
  14. Sep 28, 2026
    Memorial Health University Medical Center is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Memorial Health University Medical Center · Savannah, United StatesContact added L•••@hcahealthcare.com · •••7887Contact added (no phone or email listed)
  15. Sep 25, 2026
    Memorial Health University Medical Center is now Suspended
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Memorial Health University Medical Center · Savannah, United StatesContact removed L•••@hcahealthcare.com · •••7887Contact removed (no phone or email listed)

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 ↗

10

Registry details

Key details

Study ID
NCT05828069
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Apr 25, 2023
Start date
Mar 28, 2024
Primary completion
Sep 30, 2028 (estimated)
Completion
Sep 30, 2028 (estimated)
Last update
Oct 30, 2026

Study contacts

Carl E Allen
principal investigator · Children's Oncology Group

Oversight

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

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Tovorafenib

Other studies in this condition

Histiocytosis, Langerhans-Cell →

Other studies from this sponsor

National Cancer Institute (NCI) →

Start the discussion