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

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02122913
Recruitment Status : Active, not recruiting
First Posted : April 25, 2014
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE April 16, 2014
First Posted Date  ICMJE April 25, 2014
Last Update Posted Date June 17, 2020
Actual Study Start Date  ICMJE May 4, 2014
Actual Primary Completion Date February 1, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
  • Number of participants with adverse events [ Time Frame: 25 months ]
  • Severity of adverse events [ Time Frame: 25 months ]
    The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.
  • Maximum tolerated dose (MTD) [ Time Frame: 25 months ]
  • Recommended dose for dose expansion [ Time Frame: 25 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • The maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation.[Phase 1a] [ Time Frame: 12 months [Estimated] ]
  • Response Rate [Phase 1b] [ Time Frame: 12 months [Estimated] ]
    Anti-tumor activity of LOXO-101 in subjects who have an NTRK alteration.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2019)
  • Maximum concentration of larotrectinib in plasma (Cmax) [ Time Frame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 ]
  • Time to maximum concentration of larotrectinib in plasma (Tmax) [ Time Frame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 ]
  • Half-life of larotrectinib in plasma (t1/2) [ Time Frame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 ]
  • Area under the concentration versus time curve of larotrectinib in plasma (AUC) [ Time Frame: Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1 ]
  • Overall Response Rate (ORR) [ Time Frame: Up to 60 months ]
    Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate
  • Duration of Response (DOR) [ Time Frame: Up to 60 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2014)
  • Pharmacokinetic parameters of LOXO-101 including Cmax, Tmax, t1/2, and AUC following both QD and BID dosing. [Phase 1b] [ Time Frame: 12 months [Estimated] ]
  • Progression Free Survival [Phase 1b] [ Time Frame: 6 and 12 months [Estimated] ]
    Progression-free survival at 6 and 12 months
  • The maximum tolerated dose (MTD) [Phase 1b] [ Time Frame: 12 months [Estimated] ]
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 Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer
Official Title  ICMJE A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors
Brief Summary 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.
Detailed Description

The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in subjects with advanced solid tumors will be followed by an expansion phase in subjects with solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumors Harboring NTRK Fusion
Intervention  ICMJE Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101
Study Arms  ICMJE
  • Experimental: Tumor patients_Dose 1
    Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Dose 2
    Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Dose 3
    Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Dose 4
    Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Dose 5
    Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Dose 6
    Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).
    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
  • Experimental: Tumor patients_Expansion

    Adults patients with solid tumors and neurotrophic tyrosine kinase (NTRK) genes or proteins of types 1 - 3 (dose expansion cohort).

    Patients receive either the recommended or maximum tolerated dose of BAY2757556 as determined in the dose escalation part.

    Intervention: Drug: Larotrectinib (Vitrakvi, BAY2757556)
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 5, 2019)
75
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2014)
146
Estimated Study Completion Date  ICMJE March 30, 2021
Actual Primary Completion Date February 1, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adult patients with a locally advanced or metastatic 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
  • Proof of a malignancy harboring a NTRK fusion
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of at least 3 months
  • Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

  • Patients with unstable primary central-nervous-system tumors or metastasis, exceptions possible
  • Clinically significant active cardiovascular disease or history of myocardial infarction
  • Active uncontrolled systemic bacterial, viral, or fungal infection
  • Current treatment with a strong CYP3A4 inhibitor or inducer
  • Pregnancy or lactation
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02122913
Other Study ID Numbers  ICMJE 20288
LOXO-TRK-14001 ( Other Identifier: Loxo Inc. )
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 June 2020

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