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

• ClinicalTrials.gov Identifier: NCT03834961
• Recruitment Status: Active, not recruiting
• First Posted: February 8, 2019
• Last Update Posted: March 22, 2024
• Sponsor: Children's Oncology Group
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Children's Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Central Nervous System Neoplasm; Infantile Fibrosarcoma; Recurrent Acute Leukemia; Refractory Acute Leukemia; Solid Neoplasm	Drug: Larotrectinib Sulfate	Phase 2

Detailed Description:

PRIMARY OBJECTIVE:

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

SECONDARY OBJECTIVES:

I. 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:

I. 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.

V. 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.

X. 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 2 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Larotrectinib (LOXO-101, NSC# 788607) for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias
• Actual Study Start Date: October 25, 2019
• Estimated Primary Completion Date: September 30, 2024
• Estimated Study Completion Date: September 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment (larotrectinib); Patients 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.	Drug: Larotrectinib Sulfate; Given PO or via NG or G tube; Other Names: ARRY 470 Sulfate; LOXO 101 Sulfate; LOXO-101 Sulfate; Vitrakvi

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) of children with infantile fibrosarcoma (IFS) treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   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.

Secondary Outcome Measures :

1. Event-free survival (EFS) of children with IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   Will be computed one year after the last enrollment in a stratum.
2. Overall survival (OS) of children with IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   Will be computed one year after the last enrollment in a stratum.
3. Duration of response (DoR) of children with IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: From first observation of either partial response (PR) or complete response (CR) until either the first observation of progressive disease (PD) (event) or last known observation of the patient (censored observation), assessed up to 5 years ]
   Will be computed one year after the last enrollment in a stratum. Will be defined among patients with a confirmed best response of either PR and CR.
4. ORR of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   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.
5. EFS of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   Will be computed one year after the last enrollment in a stratum.
6. OS of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: Up to 5 years ]
   Will be computed one year after the last enrollment in a stratum.
7. DoR of children with newly diagnosed TRK fusion solid tumors other than IFS treated with neoadjuvant larotrectinib prior to local control [ Time Frame: From first observation of either partial response (PR) or complete response (CR) until either the first observation of progressive disease (PD) (event) or last known observation of the patient (censored observation), assessed up to 5 years ]
   Will be computed one year after the last enrollment in a stratum. Will be defined among patients with a confirmed best response of either PR and CR.
8. Incidence of adverse events [ Time Frame: Up to 5 years ]
   Per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. A patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the attribution(s) to the study regimen.
9. Percentage of patients with TRK fusion solid tumors with detectable circulating tumor deoxyribonucleic acid (DNA) [ Time Frame: Baseline up to 5 years ]
   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 will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). In cases of treatment resistance, we will also perform exploratory deep sequencing of ctDNA to determine whether this method can detect the emergence of resistance mutations.

Eligibility Criteria

• Ages Eligible for Study: up to 30 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.

    • 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. The duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.
  • 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).

• 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.

Contacts and Locations

Locations

United States, Alabama

Children's Hospital of Alabama

Birmingham, Alabama, United States, 35233

United States, Arkansas

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202-3591

United States, California

Kaiser Permanente Downey Medical Center

Downey, California, United States, 90242

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Kaiser Permanente-Oakland

Oakland, California, United States, 94611

Children's Hospital of Orange County

Orange, California, United States, 92868

UCSF Medical Center-Mission Bay

San Francisco, California, United States, 94158

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

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

Denver, Colorado, United States, 80218

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06520

United States, Delaware

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States, 19803

United States, District of Columbia

MedStar Georgetown University Hospital

Washington, District of Columbia, United States, 20007

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Florida

Broward Health Medical Center

Fort Lauderdale, Florida, United States, 33316

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States, 33908

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States, 32610

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States, 32207

Jackson Memorial Hospital-Holtz Children's Hospital

Miami, Florida, United States, 33136

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States, 33136

Nicklaus Children's Hospital

Miami, Florida, United States, 33155

Nemours Children's Hospital

Orlando, Florida, United States, 32827

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

Tampa, Florida, United States, 33607

United States, Georgia

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States, 30322

United States, Hawaii

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States, 96826

United States, Idaho

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States, 83712

United States, Illinois

Saint Jude Midwest Affiliate

Peoria, Illinois, United States, 61637

United States, Indiana

Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Iowa

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States, 52242

United States, Kentucky

Norton Children's Hospital

Louisville, Kentucky, United States, 40202

United States, Louisiana

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States, 70121

United States, Maryland

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21215

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

C S Mott Children's Hospital

Ann Arbor, Michigan, United States, 48109

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States, 49503

Bronson Methodist Hospital

Kalamazoo, Michigan, United States, 49007

United States, Minnesota

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States, 55455

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Missouri

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States, 64108

Cardinal Glennon Children's Medical Center

Saint Louis, Missouri, United States, 63104

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Mercy Hospital Saint Louis

Saint Louis, Missouri, United States, 63141

United States, Nebraska

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States, 68114

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, New Hampshire

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Morristown Medical Center

Morristown, New Jersey, United States, 07960

United States, New York

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467

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

New York, New York, United States, 10032

United States, North Carolina

Mission Hospital

Asheville, North Carolina, United States, 28801

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States, 28203

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States, 28204

United States, Ohio

Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Dayton Children's Hospital

Dayton, Ohio, United States, 45404

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, United States, 18103

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States, 19134

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, Rhode Island

Rhode Island Hospital

Providence, Rhode Island, United States, 02903

United States, South Carolina

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States, 29605

United States, Tennessee

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

United States, Texas

Dell Children's Medical Center of Central Texas

Austin, Texas, United States, 78723

Medical City Dallas Hospital

Dallas, Texas, United States, 75230

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States, 75390

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States, 77030

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States, 78229

United States, Utah

Primary Children's Hospital

Salt Lake City, Utah, United States, 84113

United States, Virginia

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States, 23507

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States, 99204

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States, 98405

United States, Wisconsin

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53792

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States, 54449

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Quebec

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada, H3T 1C5

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Theodore W Laetsch; Children's Oncology Group

  Study Documents (Full-Text)

Documents provided by Children's Oncology Group:

Informed Consent Form  [PDF] October 13, 2022

More Information

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT03834961
• Other Study ID Numbers: ADVL1823; NCI-2019-00015 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); ADVL1823 ( Other Identifier: Children's Oncology Group ); ADVL1823 ( Other Identifier: CTEP ); U10CA180886 ( U.S. NIH Grant/Contract )
• First Posted: February 8, 2019
• Last Update Posted: March 22, 2024
• Last Verified: March 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Children's Oncology Group:

Larotrectinib; TRK fusion; NTRK fusion; Infantile fibrosarcoma

Additional relevant MeSH terms:

Leukemia; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Fibrosarcoma; Acute Disease; Neoplasms by Histologic Type; Hematologic Diseases; Disease Attributes; Pathologic Processes; Neoplasms by Site; Nervous System Diseases; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma