Clinical Trials /

A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

NCT02576431

Description:

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors
  • Official Title: A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors

Clinical Trial IDs

  • ORG STUDY ID: 20289
  • SECONDARY ID: LOXO-TRK-15002
  • SECONDARY ID: 2015-003582-28
  • NCT ID: NCT02576431

Conditions

  • Solid Tumors Harboring NTRK Fusion

Interventions

DrugSynonymsArms
BAY2757556 (Larotrectinib, Vitrakvi)LOXO-101Arm 10_Lung cancer

Purpose

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Detailed Description

      The primary objective of this study is to investigate the efficacy of larotrectinib for the
      treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor
      kinase (NTRK) of types 1-3 in children and adults.

      Secondary objectives comprise the efficacy and safety of larotrectinib in different
      NTRK-tumor types.
    

Trial Arms

NameTypeDescriptionInterventions
Arm 1_NSCLCExperimentalPatients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 2_ThyroidExperimentalPatients with solid thyroid tumors harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 3_SarcomaExperimentalPatients with soft-tissue sarcoma harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 4_ColorectalExperimentalPatients with solid colorectal tumors harboring NTRK fusions
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 5_SalivaryExperimentalPatients with solid salivary tumors harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 6_BiliaryExperimentalPatients with solid biliary tumors harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 7_Primary CNSExperimentalPatients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 8_Other tumorsExperimentalPatients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 9_Solid tumors without confirmed NTRK fusionExperimentalPatients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 10_Lung cancerExperimentalPatients with lung cancer harboring NTRK fusions
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 11_MelanomaExperimentalPatients with melanoma harboring NTRK fusions
  • BAY2757556 (Larotrectinib, Vitrakvi)
Arm 12_Breast cancerExperimentalPatient with non-secretory breast cancer harboring NTRK fusions
  • BAY2757556 (Larotrectinib, Vitrakvi)

Eligibility Criteria

        Inclusion Criteria:

          -  Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion
             identified through molecular assays

          -  Subjects must have received prior standard therapy appropriate for their tumor type
             and stage of disease, or in the opinion of the investigator, would be unlikely to
             tolerate or derive clinically meaningful benefit from appropriate standard of care
             therapy

          -  Subjects must have at least one measurable lesion as defined by RECIST v1.1

        Exclusion Criteria:

          -  Prior progression while receiving approved or investigational tyrosine kinase
             inhibitors targeting TRK. Subjects who received less than 28 days of treatment and
             discontinued because of intolerance or toxicity are eligible.

          -  Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain
             metastases are eligible to participate in the study.) Subjects with primary CNS tumors
             are eligible.

          -  Active uncontrolled systemic bacterial, viral, or fungal infection, unstable
             cardiovascular disease, or other systemic disease that would limit compliance with
             study procedures.

          -  Pregnancy or lactation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response rate by IRC
Time Frame:Up to 120 months
Safety Issue:
Description:Proportion of subjects with either complete response or partial response as determined by an independent radiology committee (IRC) using RECIST or RANO criteria.

Secondary Outcome Measures

Measure:Best overall response rate by investigator
Time Frame:Up to 120 months
Safety Issue:
Description:Proportion of subjects with either complete response or partial response as determined by the treating investigator using RECIST or RANO criteria.
Measure:Duration of response (DOR) by IRC
Time Frame:Up to 120 months
Safety Issue:
Description:Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by an independent radiology committee (IRC).
Measure:Duration of response (DOR) by investigator
Time Frame:Up to 120 months
Safety Issue:
Description:Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by the treating investigator.
Measure:Clinical benefit rate (CBR)
Time Frame:Up to 120 months
Safety Issue:
Description:Proportion of subjects with best overall response of complete response, partial response or stable disease lasting 16 or more weeks following the initiation of larotrectinib.
Measure:Progression-free survival (PFS) after Larotrectinib
Time Frame:Up to 120 months
Safety Issue:
Description:Number of months from initiation of larotrectinib to either disease progression or death due to any cause.
Measure:Overall survival time
Time Frame:Up to 120 months
Safety Issue:
Description:Number of months from the initiation of larotrectinib to the date of death due to any cause.
Measure:Progression-free survival (PFS) after past cancer therapy
Time Frame:Up to 120 months
Safety Issue:
Description:Number of months from initiation of the line of therapy preceding larotrectinib to either disease progression or death due to any cause.
Measure:Number of subjects with adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Number of subjects with serious adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Number of subjects with treatment-related adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Severity of adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Severity of serious adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Severity of treatment-related adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Duration of adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Duration of serious adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Duration of treatment-related adverse events
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Proportion of subjects that has any tumor regression as a best response
Time Frame:Up to 120 months
Safety Issue:
Description:
Measure:Concordance coefficient
Time Frame:Up to 120 months
Safety Issue:
Description:Describes the concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor and a diagnostic test being evaluated by the sponsor

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Non-small cell lung cancer
  • Thyroid cancer
  • Sarcoma
  • Colorectal cancer
  • Salivary gland cancer
  • Biliary cancer
  • Central nervous system (CNS) Tumor
  • Breast cancer
  • Melanoma
  • Neurotrophic tyrosine receptor kinase (NTRK)
  • NTRK1
  • NTRK2
  • NTRK3
  • Fusion Positive
  • TRK fusion
  • TRKA
  • TRKB
  • TRKC
  • ETV6

Last Updated

December 11, 2020