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 an experimental 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: Study of LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion Positive Solid Tumors (NAVIGATE)
  • Official Title: A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 (Larotrectinib) in Subjects With NTRK Fusion-Positive Tumors

Clinical Trial IDs

  • ORG STUDY ID: LOXO-TRK-15002
  • NCT ID: NCT02576431

Conditions

  • Carcinoma, Non-Small-Cell Lung
  • Thyroid Neoplasms
  • Sarcoma
  • Colorectal Neoplasms
  • Salivary Gland Neoplasms
  • Biliary Tract Neoplasms
  • Brain Neoplasm, Primary
  • Carcinoma, Ductal, Breast
  • Melanoma
  • Solid Tumors
  • Glioblastoma
  • Bile Duct Neoplasms
  • Astrocytoma
  • Head and Neck Squamous Cell Carcinoma
  • Pontine Glioma
  • Pancreatic Neoplasms
  • Ovarian Neoplasms
  • Carcinoma, Renal Cell
  • Cholangiocarcinoma
  • Carcinoma
  • Carcinoma, Bronchogenic
  • Bronchial Neoplasms
  • Lung Neoplasms
  • Respiratory Tract Neoplasms
  • Thoracic Neoplasms
  • Neoplasms, Nerve Tissue
  • Nevi and Melanomas

Interventions

DrugSynonymsArms
LOXO-101Non Small Cell Lung Cancer

Purpose

Phase II, multi-center, open-label study of patients with advanced solid tumors harboring a fusion of NTRK1, NTRK2 or NTRK3.

Detailed Description

      This is a Phase II, multi-center, open-label study of patients with advanced solid tumors
      harboring a fusion of NTRK1, NTRK2 or NTRK3. Patients with NTRK1, NTRK2 or NTRK3
      fusion-positive cancers will be identified through molecular assay.

      LOXO-101 will be administered orally at 100mg twice daily (BID), with each cycle consisting
      of 28 days of dosing administered on a continuous basis.

      The study will analyze 8 cohorts of patients with tumors bearing NTRK fusions, including non
      small cell lung cancer, thyroid cancer, sarcoma, colorectal cancer, salivary gland cancer,
      biliary cancer and primary CNS tumor, as well as a cohort that will enroll patients not
      included in the histologies listed above.
    

Trial Arms

NameTypeDescriptionInterventions
Non Small Cell Lung CancerOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
ThyroidOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
SarcomaOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
ColorectalOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
SalivaryOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
BiliaryOtherAdult Solid Tumors Measurable Disease by RECIST 1.1 Oral LOXO-101
  • LOXO-101
Primary CNSOtherBrain Tumor Measurable by RANO Oral LOXO-101
  • LOXO-101
All Other Solid TumorsOtherTumor Histology not in Cohorts 1-7 Evaluable but not Measurable Disease Oral LOXO-101
  • LOXO-101

Eligibility Criteria

        Key Inclusion Criteria:

          1. Locally-advanced or metastatic malignancy with an NTRK1, NTRK2 or NTRK3 gene fusion,
             identified through molecular assays as routinely performed at CLIA or other
             similarly-certified laboratories.

          2. 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 clinical benefit from appropriate standard of care therapy.

          3. Adequate organ function as defined by the following criteria:

               -  Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) < 2.5
                  upper limit of normal (ULN), or AST and ALT < 5 ULN if liver function
                  abnormalities are due to underlying malignancy.

               -  Total bilirubin < 2.5 ULN. Subjects with a known history of Gilberts Disease and
                  an isolated elevation of indirect bilirubin are eligible.

               -  Serum creatinine < 2.0 ULN OR an estimated glomerular filtration rate ≥ 30
                  mL/minute using the Cockroft-Gault formula.

        Key Exclusion Criteria:

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

Primary Outcome Measures

Measure:Overall Response Rate of confirmed CR or PR as determined by an Independent Radiology Committee using RECIST 1.1 or RANO criteria
Time Frame:Up to 30 Months
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Overall Response Rate of confirmed CR or PR as determined by the treating investigator using RECIST 1.1 or RANO criteria
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Duration of response for subjects with best overall response of confirmed CR or PR by Independent Radiology Committee
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Duration of response for subjects with best overall response of confirmed CR or PR by the treating investigator
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Progression Free Survival
Time Frame:Up to 30 months
Safety Issue:
Description:Number of moths from initiation of Loxo-101 to the earlier of diease progression or death due to any cause
Measure:Overall Survival (OS)
Time Frame:Through study completion up to 42 months
Safety Issue:
Description:Number of months from the initiation of LOXO-101 to the date of death due to any cause.
Measure:Comparison of Progression Free Survival following initiation of Loxo-101 to that following the line of therapy immediately preceding Loxo-101
Time Frame:UP to 30 months
Safety Issue:
Description:In each subject who has received prior therapy
Measure:Incidence of Adverse Events
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Severity of Adverse Events
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Duration of Adverse Events
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Changes from baseline in clinical safety laboratory values
Time Frame:Up to 30 months
Safety Issue:
Description:
Measure:Changes from baseline in vital signs
Time Frame:Up to 30 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Loxo Oncology, Inc.

Trial Keywords

  • NTRK Fusion Positive
  • LOXO-101
  • Loxo
  • TRK
  • TRK Fusion
  • NTRK1
  • NTRK2
  • NTRK3
  • TRKA
  • TRKB
  • TRKC
  • ETV6
  • NTRK
  • larotrectinib
  • fusion
  • tumors
  • CNS tumors
  • solid tumors
  • central nervous system tumors
  • solid CNS tumors
  • primary CNS tumor
  • Advanced CNS tumor
  • Metastatic CNS tumor
  • NTRK1 fusion
  • NTRK2 fusion
  • NTRK3 fusion
  • ETV6-NTRK3
  • ETV6 fusion

Last Updated

September 5, 2017