New drug shows promise for rare childhood cancers

NCT ID NCT03834961

Disease control Sponsor: Children's Oncology Group Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study tests a drug called larotrectinib in children and young adults (up to age 30) with certain cancers that have a specific genetic change called a TRK fusion. The goal is to see if the drug can shrink solid tumors or control leukemia that has returned. The drug works by blocking signals that help these cancer cells grow.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

33 people

The number who actually took part.

Started

Oct 2019

Expected to finish

Jul 2027

An estimate. End dates often move.

Lead sponsor

A research network

The lead sponsor is a research network or cooperative group.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

Up to 30 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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. * 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.

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Conditions

The condition(s) this trial relates to.

acute leukemia central nervous system cancer central nervous system neoplasm congenital fibrosarcoma neoplasm

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Central nervous system neoplasm Infantile fibrosarcoma Recurrent acute leukemia Refractory acute leukemia Solid neoplasm

Contacts and locations

Locations

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States
Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States
BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States
Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States
Broward Health Medical Center

Fort Lauderdale, Florida, 33316, United States
C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States
Cardinal Glennon Children's Medical Center

St Louis, Missouri, 63104, United States
Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States
Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada
Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States
Children's Hospital Colorado

Aurora, Colorado, 80045, United States
Children's Hospital Los Angeles

Los Angeles, California, 90027, United States
Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States
Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States
Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States
Children's Hospital of Orange County

Orange, California, 92868, United States
Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States
Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States
Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States
Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States
Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States
Dayton Children's Hospital

Dayton, Ohio, 45404, United States
Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States
Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States
Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States
IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada
Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States
Kaiser Permanente-Oakland

Oakland, California, 94611, United States
Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States
Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103, United States
Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States
Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, 98405, United States
Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States
MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States
Medical City Dallas Hospital

Dallas, Texas, 75230, United States
Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States
Mission Hospital

Asheville, North Carolina, 28801, United States
Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States
Morristown Medical Center

Morristown, New Jersey, 07960, United States
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States
Nationwide Children's Hospital

Columbus, Ohio, 43205, United States
Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States
Nemours Children's Hospital

Orlando, Florida, 32827, United States
Nicklaus Children's Hospital

Miami, Florida, 33155, United States
Norton Children's Hospital

Louisville, Kentucky, 40202, United States
Novant Health Presbyterian Medical Center

Charlotte, North Carolina, 28204, United States
Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States
Oregon Health and Science University

Portland, Oregon, 97239, United States
Primary Children's Hospital

Salt Lake City, Utah, 84113, United States
Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States
Rhode Island Hospital

Providence, Rhode Island, 02903, United States
Riley Hospital for Children

Indianapolis, Indiana, 46202, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, 80218, United States
Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States
Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, 33607, United States
Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States
Saint Jude Midwest Affiliate

Peoria, Illinois, 61637, United States
Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States
Seattle Children's Hospital

Seattle, Washington, 98105, United States
Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States
UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States
UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States
University of Florida Health Science Center - Gainesville

Gainesville, Florida, 32610, United States
University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States
University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States
University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States
University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States
University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States
University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792, United States
Washington University School of Medicine

St Louis, Missouri, 63110, United States
Yale University

New Haven, Connecticut, 06520, United States

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