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A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer



This research study is done to test the safety of the drug larotrectinib in adult cancer patients. The drug may be used to treat cancer with a change in a particular gene (NTRK1, NTRK2 or NTRK3), because it blocks the action of these genes in cancer cells. The study also investigates how the drug is absorbed and processed in the human body. This is the first study to test larotrectinib in humans with cancer, for whom no other effective therapy exists.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting


Phase 1

Trial Eligibility



  • Brief Title: Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors
  • Official Title: A Phase 1 Study of the Oral TRK Inhibitor LOXO-101 in Adult Patients With Solid Tumors

Clinical Trial IDs

  • NCT ID: NCT02122913


  • Unspecified Adult Solid Tumor, Protocol Specific




This is a multicenter, open-label, Phase 1 study of orally administered larotrectinib in adult subjects with advanced solid tumors and a NTRK1, NTRK2, or NTRK3 gene fusion that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists.

Detailed Description

      The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in
      subjects with advanced solid tumors. This will be followed by an expansion phase in solid
      tumor subjects with an NTRK fusion. During the escalation phase, larotrectinib will be taken
      once daily (QD) or twice daily (BID). During the expansion phase, the larotrectinib dose
      selected from the escalation phase will be explored in approximately 40 additional subjects.
      Enrollment into the dose esclation portion of this study has been completed and is currently
      closed to enrollment. Patients will continue to be considered for enrollment into the dose
      expansion portion of this study.

      The objectives of the dose escalation phase are to determine the safety, tolerability,
      pharmacokinetic profile, and recommended dose of orally administered larotrectinib. The
      objectives of the expansion phase are to better characterize the safety and efficacy of
      larotrectinib in patients with NTRK fusions.

Trial Arms

LarotrectinibExperimentalEscalation- Multiple doses of larotrectinib. Expansion- The MTD dose and/or the appropriate dose for furher clinical investigation of larotrectinib found during the Escalation Phase.
  • Larotrectinib

Eligibility Criteria

        Escalation Phase [Inclusion]

          -  Locally advanced or metastatic adult solid tumor that has progressed or was
             nonresponsive to available therapies, are unfit for standard chemotherapy or for which
             no standard or available curative therapy exists;

          -  ECOG score of 0, 1 or 2;

          -  Adequate hematologic, hepatic, and renal function;

        Expansion Phase [Inclusion]

          -  Escalation Phase inclusion criteria

          -  Evidence of the NTRK fusion as previously determined with prior testing from a
             Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent certified

        Exclusion (for both Escalation and Expansion)

        • Current treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer (EIAEDs
        and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed)
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation.[Escalation]
Time Frame:32 months [Actual]
Safety Issue:
Description:Assessed by clinical review of all relevant parameters including AEs, SAEs, laboratory values, virals signs, ECG results, concomitant medications and thyroid function.

Secondary Outcome Measures

Measure:Pharmacokinetic parameters of LOXO-101 including Cmax, Tmax, t1/2, and AUC following both QD and BID dosing.
Time Frame:19 months [Estimated]
Safety Issue:
Measure:Overall Response Rate
Time Frame:Up to 60 months
Safety Issue:
Description:As assessed using RECIST 1.1 or RANO, as appropriate, per tumor type
Measure:Duration of Response
Time Frame:Up to 60 months
Safety Issue:


Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loxo Oncology, Inc.

Trial Keywords

  • TRK
  • TRKA
  • TRKB
  • TRKC
  • NTRK1
  • NTRK2
  • NTRK3
  • larotrectinib
  • NTRK fusion positive
  • NTRK gene rearrangements
  • NTRK1 fusion
  • NTRK2 fusion
  • NTRK3 fusion
  • NTRK1 gene rearrangement
  • NTRK2 gene rearrangement
  • NTRK3 gene rearrangement
  • ETV6-NTRK3
  • fusion
  • tumors
  • solid tumors
  • CNS tumors
  • central nervous system tumors
  • TRK fusion
  • ETV6
  • ETV6 fusion
  • ETV6 gene rearrangement
  • solid CNS tumor
  • Advanced CNS tumor
  • Primary CNS tumor
  • Metastatic CNS tumor
  • LOXO-101

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