Larotrectinib in Treating Patients With Previously Untreated TRK Fusion Solid Tumors and TRK Fusion Relapsed Acute Leukemia
Larotrectinib (LOXO-101, NSC# 788607) for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias
3 other identifiers
interventional
33
2 countries
80
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2019
Longer than P75 for phase_2
80 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 22, 2019
CompletedFirst Posted
Study publicly available on registry
February 8, 2019
CompletedStudy Start
First participant enrolled
October 25, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 30, 2024
CompletedResults Posted
Study results publicly available
December 2, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 25, 2027
ExpectedDecember 2, 2025
November 1, 2025
4.9 years
January 22, 2019
September 16, 2025
November 18, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (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.
Up to 5 years
Secondary Outcomes (9)
Event-free Survival (EFS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control
Up to 1 year
Overall Survival (OS) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control
Up to 1 year
Duration of Response (DoR) of Children With IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control
Up to 5 years
ORR of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control
Up to 5 years
EFS of Children and Adults With Newly Diagnosed TRK Fusion Solid Tumors Other Than IFS Treated With Neoadjuvant Larotrectinib Prior to Local Control
Up to 1 year
- +4 more secondary outcomes
Study Arms (1)
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.
Interventions
Given PO or via NG or G tube
Eligibility Criteria
You may qualify if:
- 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.
- +2 more criteria
You may not qualify if:
- 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).
- +34 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Children's Oncology Grouplead
- National Cancer Institute (NCI)collaborator
Study Sites (80)
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Denver, Colorado, 80218, United States
Yale University
New Haven, Connecticut, 06520, United States
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Broward Health Medical Center
Fort Lauderdale, Florida, 33316, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
University of Florida Health Science Center - Gainesville
Gainesville, Florida, 32610, United States
Nemours Children's Clinic-Jacksonville
Jacksonville, Florida, 32207, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
Nemours Children's Hospital
Orlando, Florida, 32827, United States
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826, United States
Saint Luke's Cancer Institute - Boise
Boise, Idaho, 83712, United States
Saint Jude Midwest Affiliate
Peoria, Illinois, 61637, United States
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital
Grand Rapids, Michigan, 49503, United States
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Cardinal Glennon Children's Medical Center
St Louis, Missouri, 63104, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, 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
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Mission Hospital
Asheville, North Carolina, 28801, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Novant Health Presbyterian Medical Center
Charlotte, North Carolina, 28204, United States
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health and Science University
Portland, Oregon, 97239, United States
Lehigh Valley Hospital-Cedar Crest
Allentown, Pennsylvania, 18103, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
Rhode Island Hospital
Providence, Rhode Island, 02903, United States
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229, United States
Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Providence Sacred Heart Medical Center and Children's Hospital
Spokane, Washington, 99204, United States
Mary Bridge Children's Hospital and Health Center
Tacoma, Washington, 98405, United States
University of Wisconsin Carbone Cancer Center - University Hospital
Madison, Wisconsin, 53792, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Related Publications (1)
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.
PMID: 39652801DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Results Reporting Coordinator
- Organization
- Children's Oncology Group
Study Officials
- PRINCIPAL INVESTIGATOR
Theodore W Laetsch
Children's Oncology Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 22, 2019
First Posted
February 8, 2019
Study Start
October 25, 2019
Primary Completion
September 30, 2024
Study Completion (Estimated)
July 25, 2027
Last Updated
December 2, 2025
Results First Posted
December 2, 2025
Record last verified: 2025-11