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ADVL1823: Larotrectinib (LOXO-101) in Children with TRK Fusion Solid Tumors and Relapsed Leukemia

Larotrectinib for Previously Untreated TRK Fusion Pediatric Solid Tumors and TRK Fusion Relapsed Pediatric Acute Leukemias


Solid Tumor

Phase I/II

Leukemia / Lymphoma

Diseases Treated:

Solid Tumors 

Eligibility Overview:

  • 21 years old or younger (at St. Jude)
  • Newly diagnosed infantile fibrosarcoma  or solid tumor with NTRK1, NTRK2 or NTRK3 fusion OR
  • Relapsed/refractory acute leukemia with NTRK1, NTRK2 or NTRK3 fusion
  1. Brief Summary

    Larotrectinib is a highly selective oral small molecule inhibitor of the TRK family of tyrosine kinases which are encoded by the NTRK genes (NTRK1, NTRK2, and NTRK3). Fusions of these genes occur across a wide range of pediatric and adult malignancies and are nearly pathognomonic for infantile fibrosarcoma.

    Preclinical studies have shown that larotrectinib is active in cancer cell lines harboring TRK fusions, while having no activity in cell lines without these fusions. Ongoing clinical trials of larotrectinib in children and adults have shown a 75% objective response rate in patients with relapsed or refractory TRK fusion cancers across a wide range of tumor types, including a 93% objective response rate in children with TRK fusion cancers on a Phase I trial. This study also established a pediatric recommended Phase II dose.

    The primary cohort for this open label Phase II trial will be patients with infantile fibrosarcoma, and patients with other TRK fusion solid tumors will be analyzed in a separate cohort. This study will also include an exploratory cohort for patients with relapsed or refractory TRK fusion acute leukemias.

    Primary Objectives

    • To determine the objective response rate of children with infantile fibrosarcoma treated with neoadjuvant larotrectinib prior to local control

    Eligibility Criteria

    Inclusion criteria include:

    • 21 years old or younger
    • Diagnosed with one of the following:
      • Infantile fibrosarcoma with NTRK1, NTRK2 or NTRK3 fusion (Cohort A)
      • Solid tumor other than infantile fibrosarcoma, including CNS tumors but excluding high grade gliomas, with NTRK1, NTRK2 or NTRK3 fusion (Cohort B)
      • Relapsed or refractory acute leukemia with NTRK1, NTRK2 or NTRK3 fusion (Cohort C)
    • No prior anti-cancer therapy, including radiotherapy, other than surgical resection (Cohorts A and B) or fully recovered from acute toxic effects of all prior anti-cancer therapy (Cohort C)
    • Adequate bone marrow, liver and renal function

    Exclusion criteria include:

    • Pregnant or breastfeeding
    • Currently receiving another investigational drug
    • Currently receiving other anti-cancer agents (except leukemia patients receiving corticosteroids or hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy)
    • High Grade Glioma

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in the U.S.

  2. About this study

    This is a Phase II study of larotrectinib, a type of drug that works by blocking cell signal proteins that are thought to be important for tumors to grow. In a Phase II study, the goal is to find out what effects, good and/or bad, a drug or combination of drugs has on people with a type of cancer.

    We are using larotrectinib in this study because it has been shown to block the growth of cancer cells with TRK fusions in children and adults who have TRK fusion cancers that have not gone away or have come back after standard therapy. In children and adults with TRK fusion cancers, larotrectinib has caused tumors to shrink in most but not all patients. This study will evaluate what the effects of larotrectinib are if given at the time cancer is first diagnosed instead of standard therapy. We do not know if it will work against your cancer.

    Larotrectinib has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of children and adults with TRK fusion cancers that have spread after standard therapy, are not able to be surgically removed after standard therapy, or for whom there is no standard therapy available. Using larotrectinib to treat patients with newly diagnosed TRK fusion cancers, as is being done in this study, is still experimental.

    Purpose of this clinical trial

    The main goals of this study are to find out the good and/or bad effects larotrectinib has on your type of cancer. Researchers also want to learn more about the side effects of larotrectinib and how larotrectinib works against cancer cells.

    Eligibility Overview

    • 21 years old or younger
    • Newly diagnosed infantile fibrosarcoma or solid tumor with NTRK1, NTRK2 or NTRK3 fusion OR
    • Relapsed/refractory acute leukemia with NTRK1, NTRK2 or NTRK3 fusion
  3. ADVL1823 Quick View
    Sponsor Children's Oncology Group identifier NCT03834961
    Trial start date September 2019
    Estimated enrollment 5 (at St. Jude
    Study type Interventional
    Study phase Phase II
    Conditions nfantile fibrosarcoma, solid tumor, leukemia
    Ages Under 21 (at St. Jude
    Principal investigator Alberto Pappo, MD (at St. Jude)                       
    Study sites St. Jude Children’s Research Hospital and collaborating sites in the U.S.
    For a consultation or to discuss ADVL1823 St. Jude Physician/Patient Referral Office


St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.