LOXO-TRK: Testing Larotrectinib (LOXO-101) in Children with Advanced Solid Tumors or Brain Tumors

A Phase 1/2 Study of the Oral TRK Inhibitor LOXO-101 in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors (LOXO-TRK-15003)

Categories:

Solid Tumor

Brain Tumor

Diseases Treated:

Solid Tumors, Central Nervous System Tumors

Eligibility Overview:

Phase 1

  • 1 to 21 years of age with locally advanced or metastatic solid tumor or primary CNS tumor that has progressed or was nonresponsive to therapy and for which there is no standard or available curative therapy, OR
  • ≥ 1 month old with diagnosis of infantile/congenital fibrosarcoma or congenital mesoblastic nephroma with documented NTRK fusion that has progressed or was nonresponsive to therapy and for which there is no standard or available curative therapy

Phase 2

  • ≥ 1 month old at C1D1 with locally advanced or metastatic infantile fibrosarcoma OR
  • ≥ 1 month old through 21 years old at C1D1 with locally advanced or metastatic solid tumor or primary CNS tumor that has progressed or was not responsive to therapy and for which no standard or available curative therapy with a NTRK gene funsion OR
  • More than 21 years old with tumor diagnosis typical of a pediatric patient and an NTRK fusion
  1. Brief Summary

    Solid and central nervous system (CNS) tumors are among the more common pediatric cancers. Despite treatment advances, many tumors return or are unresponsive to standard therapy.

    Prior studies have suggested that the tropomyosin-related kinase (TRK) family of receptors plays a role in many pediatric cancers. Treatment with larotrectinib (LOXO-101), an investigational selective TRK inhibitor, has been shown to slow the growth of tumors in certain adult patients with advanced solid tumors. This St. Jude clinical trial will test the safety and effectiveness of larotrectinib in younger patients with recurrent or refractory advanced solid or primary CNS tumors.

    Phase 1 Primary Objective

    The main goal of the first phase of this study is to determine the safety of oral larotrectinib (LOXO-101) in children, adolescents and young adults with advanced solid or primary CNS tumors.

    Phase 1 Secondary Objectives

    Secondary objectives of this clinical trial are:

    • To evaluate how the body absorbs and processes different doses of larotrectinib
    • To identify the maximum tolerated dose and/or the appropriate dose of larotrectinib
    • To determine how the tumor responds to larotrectinib
    • To evaluate any side effects

    Phase 2 Primary Objective

    The main goal of the second phase of this study is to determine the overall response rate (ORR) after larotrectinib treatment in patients who have advanced cancers.

    Eligibility Criteria

    Inclusion Criteria include:

    Phase 1:

    • 1 to 21 years of age with locally advanced or metastatic solid tumor or primary CNS tumor that has progressed or was nonresponsive to therapy and for which there is no standard or available curative therapy, OR
    • ≥ 1 month old with diagnosis of infantile/congenital fibrosarcoma or congenital mesoblastic nephroma with documented NTRK fusion that has progressed or was nonresponsive to therapy and for which there is no standard or available curative therapy OR
    • Patient with locally advanced infantile fibrosarcoma who would require disfiguring surgery or limb amputation to achieve complete surgical resection
    • Karnofsky (≥ 16 years old) or Lansky (< 16 years old) performance score ≥ 50

    Phase 2:

    • ≥ 1 month old at C1D1 with locally advanced or metastatic infantile fibrosarcoma OR
    • ≥ 1 month old through 21 years old at C1D1 with locally advanced or metastatic solid tumor or primary CNS tumor that has progressed or was not responsive to therapy and for which no standard or available curative therapy with a NTRK gene fusion OR
    • More than 21 years old with tumor diagnosis typical of a pediatric patient and an NTRK fusion
    • Karnofsky (≥ 16 years old) or Lansky (< 16 years old) performance score ≥ 50

    Exclusion Criteria include:

    • Investigational agent, anticancer therapy or major surgery within 4 weeks prior to study
    • Active cardiovascular disease or history of prolonged QT interval corrected for heart rate
    • Current treatment with strong cytochrome P450 (CYP) 3A4 inhibitor or inducer

    Study Design

    Open-label, Phase 1/2

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in and outside the U.S.

  2. About this Study

    This study is being done to test the safety of a new drug called larotrectinib in children, adolescents and young adults with certain kinds of tumors that are hard to treat. These include solid tumors and brain tumors, also known as central nervous system (CNS) tumors.

    Some changes in your genes can cause certain types of cancer to grow. Larotrectinib, also known as LOXO-101 was designed to block the effect of one of these changes. larotrectinib is an investigational (experimental) drug that has not yet been approved by the U.S. Food and Drug Administration (FDA). This research study will be the first time larotrectinib will be tested in children. 

    Purpose of this Study

    The main goal of this study is to see if larotrectinib is safe to use in children. Researchers also want to figure out the best dose of larotrectinib that will kill the cancer without causing severe side effects or other problems. They also want to see how the body absorbs and processes larotrectinib. Researchers hope that the study results will help improve treatments for this type of cancer in the future.

    Eligibility Overview

    Phase 1:

    • 1 to 21 years of age with an advanced solid tumor or brain tumor that has worsened or did not respond to treatment, OR
    • At least 1 month old with fibrosarcoma diagnosed at birth or shortly after birth; or mesoblastic nephroma (kidney tumor) diagnosed at birth with NTRK gene fusion that has worsened or did not respond to treatment

    Phase 2:

    • ≥ 1 month old at C1D1 with locally advanced or metastatic infantile fibrosarcoma OR
    • ≥ 1 month old through 21 years old at C1D1 with locally advanced or metastatic solid tumor or primary CNS tumor that has progressed or was not responsive to therapy and for which no standard or available curative therapy with a NTRK gene fusion OR
    • More than 21 years old with tumor diagnosis typical of a pediatric patient and an NTRK fusion
  3. LOXO-TRK Quick View
    Sponsor Loxo Oncology, Inc.
    ClinicalTrials.gov Identifier NCT02637687
    Trial Start Date December 2015
    Estimated Enrollment 84
    Study Type Interventional
    Study Phase Phase 1/2
    Conditions Solid tumor, central nervous system tumors
    Ages 1 year or older (≥ 1 month for certain diagnoses)
    Principal Investigator Alberto Pappo, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss LOXO-TRK St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

Alberto Pappo, MD

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
Email: referralinfo@stjude.org

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.