Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02576431
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : September 17, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 15, 2015
Last Update Posted Date September 17, 2020
Actual Study Start Date  ICMJE September 30, 2015
Estimated Primary Completion Date August 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 10, 2020)
Best overall response rate by IRC [ Time Frame: Up to 120 months ]
Proportion of subjects with either complete response or partial response as determined by an independent radiology committee (IRC) using RECIST or RANO criteria.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
Best Overall Response of confirmed CR or PR as measured by RECIST 1.1 or RANO criteria as appropriate to tumor type [ Time Frame: Up to 30 Months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2020)
  • Best overall response rate by investigator [ Time Frame: Up to 120 months ]
    Proportion of subjects with either complete response or partial response as determined by the treating investigator using RECIST or RANO criteria.
  • Duration of response (DOR) by IRC [ Time Frame: Up to 120 months ]
    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).
  • Duration of response (DOR) by investigator [ Time Frame: Up to 120 months ]
    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.
  • Clinical benefit rate (CBR) [ Time Frame: Up to 120 months ]
    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.
  • Progression-free survival (PFS) after Larotrectinib [ Time Frame: Up to 120 months ]
    Number of months from initiation of larotrectinib to either disease progression or death due to any cause.
  • Overall survival time [ Time Frame: Up to 120 months ]
    Number of months from the initiation of larotrectinib to the date of death due to any cause.
  • Progression-free survival (PFS) after past cancer therapy [ Time Frame: Up to 120 months ]
    Number of months from initiation of the line of therapy preceding larotrectinib to either disease progression or death due to any cause.
  • Number of subjects with adverse events [ Time Frame: Up to 120 months ]
  • Number of subjects with serious adverse events [ Time Frame: Up to 120 months ]
  • Number of subjects with treatment-related adverse events [ Time Frame: Up to 120 months ]
  • Severity of adverse events [ Time Frame: Up to 120 months ]
  • Severity of serious adverse events [ Time Frame: Up to 120 months ]
  • Severity of treatment-related adverse events [ Time Frame: Up to 120 months ]
  • Duration of adverse events [ Time Frame: Up to 120 months ]
  • Duration of serious adverse events [ Time Frame: Up to 120 months ]
  • Duration of treatment-related adverse events [ Time Frame: Up to 120 months ]
  • Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 120 months ]
  • Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 120 months ]
  • Proportion of subjects that has any tumor regression as a best response [ Time Frame: Up to 120 months ]
  • Concordance coefficient [ Time Frame: Up to 120 months ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2015)
  • Duration of Response (DOR) [ Time Frame: Up to 30 months ]
  • Progression Free Survival (PFS) [ Time Frame: Up to 30 months ]
  • Overall Survival (OS) [ Time Frame: Through study completion up to 42 months ]
    Number of months from the initiation of LOXO-101 to the date of death due to any cause.
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 30 months ]
    To assess the safety profile and tolerability of LOXO-101
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors
Official Title  ICMJE A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors Harboring NTRK Fusion
Intervention  ICMJE Drug: BAY2757556 (Larotrectinib, Vitrakvi)
Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.
Other Name: LOXO-101
Study Arms  ICMJE
  • Experimental: Arm 1_NSCLC
    Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 2_Thyroid
    Patients with solid thyroid tumors harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 3_Sarcoma
    Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 4_Colorectal
    Patients with solid colorectal tumors harboring NTRK fusions
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 5_Salivary
    Patients with solid salivary tumors harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 6_Biliary
    Patients with solid biliary tumors harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 7_Primary CNS
    Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 8_Other tumors
    Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 9_Solid tumors without confirmed NTRK fusion
    Patients 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)
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 10_Lung cancer
    Patients with lung cancer harboring NTRK fusions
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 11_Melanoma
    Patients with melanoma harboring NTRK fusions
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
  • Experimental: Arm 12_Breast cancer
    Patient with non-secretory breast cancer harboring NTRK fusions
    Intervention: Drug: BAY2757556 (Larotrectinib, Vitrakvi)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 2, 2020)
203
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2015)
151
Estimated Study Completion Date  ICMJE September 30, 2025
Estimated Primary Completion Date August 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   China,   Czechia,   Denmark,   France,   Germany,   Hungary,   Ireland,   Italy,   Japan,   Korea, Republic of,   Poland,   Portugal,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02576431
Other Study ID Numbers  ICMJE 20289
LOXO-TRK-15002 ( Other Identifier: Loxo Oncology, Inc )
2015-003582-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Bayer
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP