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AzTrials

Central Nervous System NeoplasmPhase 2NCT03834961

Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia

A Phase 2 study testing Larotrectinib Sulfate in people with Central Nervous System Neoplasm and Infantile Fibrosarcoma, run by Children's Oncology Group at 80 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial studies the side effects and how well larotrectinib works in treating patients with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that has come back. Larotrectinib may stop the growth of cancer cells with TRK fusions by blocking the TRK enzymes needed for cell growth. Read more about this study

Who is it for?
Ages Up to 30 years
What is being tested?
Larotrectinib Sulfate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
80 sitesin 2 countries
Study dates
25 Oct 2019to 25 Jul 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must be =< 30 years of age at the time of study entry
  • COHORT A: Patients must have a histologic diagnosis of infantile fibrosarcoma with an NTRK1, NTRK2, or NTRK3 fusion identified in a Clinical Laboratory Improvement Act/College of American Pathologists (CLIA/CAP) certified laboratory. Fusions may be identified by fluorescence in situ hybridization (FISH) or molecular techniques (reverse transcriptase-polymerase chain reaction [RT-PCR] using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, an ETV6 rearrangement is sufficient for eligibility in Cohort A. Identification of the upstream TRK fusion partner is not required.
  • COHORT B: Patients must have a histologic diagnosis of any solid tumor other than infantile fibrosarcoma, including central nervous system (CNS) tumors but excluding high grade gliomas. An NTRK1, NTRK2, or NTRK3 fusion must be identified in a CLIA/CAP certified laboratory. Fusions may be identified by FISH or molecular techniques (RT-PCR using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, there must be an identified rearrangement in NTRK1, NTRK2, or NTRK3 (e.g., an ETV6 rearrangement is not sufficient for eligibility) unless the patient has a diagnosis of congenital mesoblastic nephroma in which case an ETV6 rearrangement is sufficient for eligibility. Identification of the upstream TRK fusion partner is not required.
  • COHORT C: Patients must have a histologic diagnosis of relapsed or refractory acute leukemia with an NTRK1, NTRK2, or NTRK3 fusion identified in a CLIA/CAP certified laboratory. Fusions may be identified by FISH or molecular techniques (RT-PCR using primers flanking the fusion junction or next generation sequencing). For fusions identified by FISH, there must be an identified rearrangement in NTRK1, NTRK2, or NTRK3 (e.g., an ETV6 rearrangement is not sufficient for eligibility). Identification of the upstream TRK fusion partner is not required.
  • SOLID TUMORS (COHORTS A AND B): Patients must have measurable disease. Patients must have disease that cannot be completely resected without a predicted functional, neurologic, or significant cosmetic deficit in the opinion of the investigator.
  • LEUKEMIA (COHORT C): Patients must have >= 5% blasts in the bone marrow. Extramedullary disease is permitted.
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  • Patients must have a Lansky or Karnofsky performance status score of >= 50, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age. NOTE: Neurologic deficits in patients with CNS tumors must have been stable for at least 7 days prior to study enrollment. 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.
  • COHORTS A AND B: No prior anti-cancer therapy, including radiotherapy, other than surgical resection is permitted.
  • Patients who experience recurrence after surgery alone and no other anti-cancer therapy will be eligible.
  • If not eligible due to prior anticancer therapy, patients may be eligible for the larotrectinib arm of Pediatric MATCH (APEC1621A) or treatment with commercial larotrectinib off study.
  • COHORT C: Patients with relapsed leukemia (Cohort C) must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g. blood count criteria, the patient is considered to have recovered adequately.
  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive.
  • A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine [6MP], and/or methotrexate).
  • A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment.
  • >= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.
  • Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.
  • Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil [ANC] counts): >= 7 days after the last dose of agent.
  • Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.
  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.
  • Hematopoietic growth factors: >= 14 days after the last dose of a long-acting growth factor (e.g. pegfilgrastim) or 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator.
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): >= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors ).
  • Stem cell infusions (with or without total body irradiation [TBI]):
  • Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: >= 84 days after infusion and no evidence of graft versus host disease (GVHD).
  • Autologous stem cell infusion including boost infusion: >= 42 days.
  • Cellular therapy: >= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer [NK] cells, dendritic cells, etc.)
  • Radiation therapy (XRT)/external beam irradiation including protons: >= 14 days after local XRT; >= 150 days after TBI, craniospinal XRT or if radiation to >= 50% of the pelvis; >= 42 days if other substantial BM radiation.
  • Radiopharmaceutical therapy (e.g., radiolabeled antibody): >= 42 days after systemically administered radiopharmaceutical therapy.
  • Patients must not have received prior exposure to TRK inhibitors (including larotrectinib, LOXO-195, entrectinib, lorlatinib, crizotinib, or lestaurtinib).
  • For patients with solid tumors without known bone marrow involvement: Peripheral absolute neutrophil count (ANC) >= 1000/mm^3 (within 7 days prior to enrollment).
  • For patients with solid tumors without known bone marrow involvement: Platelet count >= 100,000/mm^3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).
  • For patients with solid tumors without known bone marrow involvement: Hemoglobin >= 8.0 g/dL at baseline (within 7 days prior to enrollment) (may receive red blood cell [RBC] transfusions).
  • Patients with solid tumors with known bone marrow metastatic disease will be eligible for study provided they meet the blood counts above (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity.
  • For patients with leukemia: Platelet count >= 20,000/mm^3 (within 7 days prior to enrollment) (may receive platelet transfusions; must not be known to be refractory to red cell or platelet transfusion).
  • For patients with leukemia: Hemoglobin >= 8.0 g/dL at baseline (within 7 days prior to enrollment) (may receive RBC transfusions; must not be known to be refractory to red cell or platelet transfusion).
  • For patients with leukemia: These patients must not be known to be refractory to red cell or platelet transfusion.
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
  • 1 month to < 6 months (male 0.4 mg/dL, female 0.4 mg/dL)
  • 6 months to < 1 year (male 0.5 mg/dL, female 0.5 mg/dL)
  • 1 to < 2 years (male 0.6 mg/dL, female 0.6 mg/dL)
  • 2 to < 6 years (male 0.8 mg/dL, female 0.8 mg/dL)
  • 6 to < 10 years (male 1 mg/dL, female 1 mg/dL)
  • 10 to < 13 years (male 1.2 mg/dL, female 1.2 mg/dL)
  • 13 to < 16 years (male 1.5 mg/dL, female 1.4 mg/dL)
  • >= 16 years (male 1.7 mg/dL, female 1.4 mg/dL)
  • For patients < 1 month of age, serum creatinine levels must be < 1.5 x the treating institution's creatinine upper limit of normal (ULN) for patients < 1 month of age or the creatinine clearance or radioisotope GFR must be >= 70 mL/min/1.73 m^2.
  • Patients with solid tumors: Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment). After approval of the study chair or designee, infants with a higher total bilirubin due to physiologic or breast milk jaundice are eligible if the conjugated (direct) bilirubin is =< 2 mg/dL.
  • Patients with solid tumors: Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 135 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Patients with solid tumors: Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
  • Patients with leukemias: Conjugated (direct) bilirubin =< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment).
  • Patients with leukemias: SGPT (ALT) =< 225 U/L (within 7 days prior to enrollment). For the purpose of this study, the ULN for SGPT is 45 U/L.
  • Patients with leukemias: Serum albumin >= 2 g/dL (within 7 days prior to enrollment).
  • Patients with seizure disorder may be enrolled if on a stable antiepileptic regimen for >= 14 days and well controlled.
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5) except tendon reflex decreased resulting from prior therapy must be =< grade 2.
  • All patients and/or their parents or legal guardians must sign a written informed consent.
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events as seen in animal/human studies, OR because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Female patients of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method for the duration of study therapy and for at least one month after the final dose of larotrectinib. Males of reproductive potential with a non-pregnant female partner of child-bearing potential must use a highly effective contraception for the duration of the study and for at least one month after the final dose of larotrectinib. Because of the unknown risk of larotrectinib in nursing infants, nursing women should discontinue breastfeeding during treatment with larotrectinib and for 3 days following the final dose.
  • Patients with solid tumors, including CNS tumors, requiring corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. Patients with leukemia may receive systemic corticosteroids for cytoreduction up to 24 hours prior to the start of protocol therapy. If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid.
  • Patients who are currently receiving another investigational drug are not eligible.
  • Patients who are currently receiving other anti-cancer agents are not eligible [except leukemia patients receiving corticosteroids or hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy]. Patients with leukemia should receive a single dose of intrathecal cytarabine, hydrocortisone, and/or methotrexate within 7 days prior to Day 1 of Cycle 1 at the time of the baseline lumbar puncture.
  • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial.
  • Patients currently receiving a strong CYP3A4 inducer or inhibitor are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to enrollment to the end of the study. Note: CYP3A4 inducing anti-epileptic drugs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
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  • Patients with malabsorption syndrome or other conditions that significantly limit enteral absorption are not eligible.
  • Patients who are unable to swallow capsules or liquid and do not have gastric access via a nasogastric or gastrostomy tube are not eligible.
  • Patients who have an uncontrolled infection are not eligible.
  • Patients who have received prior solid organ transplantation are not eligible.
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
  • Patients with high grade gliomas (HGG) are not eligible.

Trial locations and contacts

80 sites in 2 countries.

80 sites in 2 countries

United States78 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Lehigh Valley Hospital-Cedar Crest

    Allentown, Pennsylvania, 18103

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mission Hospital

    Asheville, North Carolina, 28801

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Saint Luke's Cancer Institute - Boise

    Boise, Idaho, 83712

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Broward Health Medical Center

    Fort Lauderdale, Florida, 33316

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • University of Florida Health Science Center - Gainesville

    Gainesville, Florida, 32610

  • Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

    Grand Rapids, Michigan, 49503

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Norton Children's Hospital

    Louisville, Kentucky, 40202

  • University of Wisconsin Carbone Cancer Center - University Hospital

    Madison, Wisconsin, 53792

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • University of Miami Miller School of Medicine-Sylvester Cancer Center

    Miami, Florida, 33136

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Yale University

    New Haven, Connecticut, 06520

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Saint Jude Midwest Affiliate

    Peoria, Illinois, 61637

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Primary Children's Hospital

    Salt Lake City, Utah, 84113

  • University of Texas Health Science Center at San Antonio

    San Antonio, Texas, 78229

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Cardinal Glennon Children's Medical Center

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada2 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

Other trials in Canada

About this study

Official title: Larotrectinib (LOXO-101, NSC# 788607) for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias

This phase II trial studies the side effects and how well larotrectinib works in treating patients with previously untreated TRK fusion solid tumors and TRK fusion acute leukemia that has come back. Larotrectinib may stop the growth of cancer cells with TRK fusions by blocking the TRK enzymes needed for cell growth.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To determine the objective response rate (ORR) of children with infantile fibrosarcoma (IFS) treated with neoadjuvant larotrectinib prior to local control.

SECONDARY OBJECTIVES:

  1. To determine event-free survival (EFS), overall survival (OS), and duration of response (DoR) of children with IFS treated with neoadjuvant larotrectinib prior to local control.

II. To determine the ORR, EFS, OS, and DoR of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control.

III. To describe the toxicity of larotrectinib in children with solid tumors and acute leukemia.

IV. To determine the percentage of patients with TRK fusion solid tumors with detectable circulating tumor deoxyribonucleic acid (DNA) at baseline and after 2 weeks, 4 weeks, 24 weeks of treatment, at the time of discontinuation of larotrectinib therapy, and at progression.

EXPLORATORY OBJECTIVES:

  1. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors other than IFS treated with adjuvant larotrectinib following upfront surgery with positive margins after neoadjuvant larotrectinib.

II. To determine the EFS, OS, and DoR of children with TRK fusion solid tumors who experience a complete response to larotrectinib and subsequently discontinue larotrectinib therapy.

III. To determine the remission induction rate for patients with recurrent/refractory TRK fusion leukemia when treated with larotrectinib.

IV. To evaluate the surgical morbidity and extent of resection of initially unresectable tumors in patients with TRK fusion solid tumors who undergo surgical resection following neoadjuvant larotrectinib.

  1. To evaluate mechanisms of response and resistance to larotrectinib in children with TRK fusion cancers.

VI. To evaluate the morphologic features of TRK fusion solid tumors at time of initial biopsy to further define criteria for pathologic diagnosis of these tumors.

VII. To evaluate immunohistochemistry for pan-TRK as a screening method for TRK fusion tumors and in resection specimens following neoadjuvant treatment with larotrectinib.

VIII. To evaluate the histologic response to larotrectinib in resection specimens following neoadjuvant treatment.

IX. To evaluate circulating tumor DNA for the detection of the emergence of resistance mutations and recurrence in patients with TRK fusion solid tumors treated with larotrectinib.

  1. To evaluate the ratio of cerebrospinal fluid (CSF) to concurrent plasma concentrations of larotrectinib in patients with leukemia.

XI. To evaluate the change in neurocognitive/behavioral functioning over time between baseline and 5 years post-diagnosis of patients treated on this protocol using parent-reported adaptive functioning (Adaptive Behavior Assessment System [ABAS]-III General Adaptive Composite), executive function (Behavior Rating Inventory of Executive Function Scales-Preschool Version [BRIEF-P] or BRIEF-2 Global Executive Composite Score), psychosocial functioning (Behavior Assessment System for Children [BASC]-3 Internalizing, Externalizing and Behavioral Symptoms Indices) and quality of life (Pediatric Quality of Life Inventory [PedsQL] Total score).

OUTLINE:

Patients receive larotrectinib orally (PO) or by nasogastric (NG) or gastric tube (G-tube) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients whose tumors shrink sufficiently while taking larotrectinib may undergo surgical resection of their tumor while on study.

After completion of study treatment, patients are followed up at 3, 6, 12, 18, 24, 30, 36, and 48 months and annually thereafter for up to 5 years from the date of study entry.

Being tested
Larotrectinib Sulfate
Keywords
Larotrectinib, TRK fusion, NTRK fusion, Infantile fibrosarcoma
Medical subject headings
Central Nervous System Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Larotrectinib SulfateDrug

    Also called ARRY 470 Sulfate, LOXO 101 Sulfate, LOXO-101 Sulfate, Vitrakvi

    Given PO or via NG or G tube

Study groups in NCT03834961
Study groupRoleWhat they receive
Treatment (larotrectinib)ExperimentalPatients receive larotrectinib PO or by NG or G-tube BID on days 1-28. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity, or complete surgical resection of tumor.
Receives: Drug: Larotrectinib Sulfate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective Response Rate (ORR) of Children With Infantile Fibrosarcoma (IFS) Treated With Neoadjuvant Larotrectinib Prior to Local Control

    A responder is defined as a patient who achieves a best response of partial response (PR) or complete response (CR) on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.

    Measured: Up to 5 years

Secondary outcomes (9)

  1. Event-free Survival (EFS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    The Kaplan-Meier method will be used to estimate 1-year EFS, defined as the time from study entry until last contact, relapse, secondary malignancy, or death.

    Measured: Up to 1 year

  2. Overall Survival (OS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    The Kaplan-Meier method will be used to estimate 1-year OS, defined as the time from study entry until last contact or death.

    Measured: Up to 1 year

  3. Duration of Response (DoR) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    Will be defined among patients with a confirmed best response of either PR and CR. Will be computed as the time from first observation of either PR or CR until either the first observation of progressive disease (PD) (event) or last known observation of the patient (censored observation).

    Measured: Up to 5 years

  4. ORR of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    A responder is defined as a patient who achieves a best response of PR or CR on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.

    Measured: Up to 5 years

  5. EFS of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    The Kaplan-Meier method will be used to estimate 1-year EFS, defined as the time from study entry until last contact, relapse, secondary malignancy, or death.

    Measured: Up to 1 year

  6. OS of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    The Kaplan-Meier method will be used to estimate 1-year OS, defined as the time from study entry until last contact or death.

    Measured: Up to 1 year

  7. DoR of Children With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control

    Will be defined among patients with a confirmed best response of either PR and CR. Will be computed as the time from first observation of either PR or CR until either the first observation of PD (event) or last known observation of the patient (censored observation).

    Measured: Up to 5 years

  8. Percentage of Participants With Adverse Events

    Will report the percentage of patients within each disease stratum who experienced a grade 3 or higher toxicity with attribution of possible, probable, or definite while on protocol therapy or within 30 days of the last dose of therapy. Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Through 30 days after treatment, a mean of 12.6 months

  9. Percentage of Patients With TRK Fusion Solid Tumors With Detectable Circulating Tumor Deoxyribonucleic Acid (ctDNA)

    The percentage of ctDNA and frequency with which patients have detectable ctDNA prior to the start of therapy and at times during therapy when subsequent serial samples are obtained (2 weeks, 4 weeks, 24 weeks of treatment, at the time of discontinuation of larotrectinib therapy, and at progression) will be calculated.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2019
  2. Study start25 Oct 2019
  3. Primary completion30 Sep 2024
  4. Study completion25 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03834961
Sponsor's protocol ID
ADVL1823
Other IDs
NCI-2019-00015, ADVL1823, ADVL1823, U10CA180886
Status last verified
Nov 2025
First submitted
22 Jan 2019
Last updated
2 Dec 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Laetsch TW, Voss S, Ludwig K, Hall D, Barkauskas DA, DuBois SG, Ronan J, Rudzinski ER, Memken A, Robinson K, Sorger J, Reid JM, Bhatla T, Crompton BD, Church AJ, Fox E, Weigel BJ. Larotrectinib for Newly Diagnosed Infantile Fibrosarcoma and Other Pediatric NTRK Fusion-Positive Solid Tumors (Children's Oncology Group ADVL1823). J Clin Oncol. 2025 Apr;43(10):1188-1197. doi: 10.1200/JCO-24-01854. Epub 2024 Dec 9.

    PubMed 39652801

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Larotrectinib Sulfate in people with Central Nervous System Neoplasm and Infantile Fibrosarcoma, run by Children's Oncology Group at 80 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 55 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 80 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) of Children With Infantile Fibrosarcoma (IFS) Treated With Neoadjuvant Larotrectinib Prior to Local Control (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03834961, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2025.

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