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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 : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Harboring NTRK Fusion Drug: Larotrectinib (Vitrakvi, BAY2757556) Phase 1

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Oral TRK Inhibitor LOXO-101 in Adult Patients With Solid Tumors
Actual Study Start Date : December 31, 2014
Actual Primary Completion Date : February 1, 2017
Estimated Study Completion Date : December 31, 2019

Arm Intervention/treatment
Experimental: Tumor patients_Dose 1
Adult patients with solid tumors receiving 50 mg of BAY2757556 once daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

Experimental: Tumor patients_Dose 2
Adult patients with solid tumors receiving 100 mg of BAY2757556 once daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

Experimental: Tumor patients_Dose 3
Adult patients with solid tumors receiving 100 mg of BAY2757556 twice daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

Experimental: Tumor patients_Dose 4
Adult patients with solid tumors receiving 200 mg of BAY2757556 once daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

Experimental: Tumor patients_Dose 5
Adult patients with solid tumors receiving 150 mg of BAY2757556 twice daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

Experimental: Tumor patients_Dose 6
Adult patients with solid tumors receiving 200 mg of BAY2757556 twice daily (dose escalation cohort).
Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101

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.

Drug: Larotrectinib (Vitrakvi, BAY2757556)
BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.
Other Name: LOXO-101




Primary Outcome Measures :
  1. Number of participants with adverse events [ Time Frame: 25 months ]
  2. Severity of adverse events [ Time Frame: 25 months ]
    The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.

  3. Maximum tolerated dose (MTD) [ Time Frame: 25 months ]
  4. Recommended dose for dose expansion [ Time Frame: 25 months ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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

  6. Duration of Response (DOR) [ Time Frame: Up to 60 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02122913


Locations
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United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106-2602
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Bayer

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02122913     History of Changes
Other Study ID Numbers: 20288
LOXO-TRK-14001 ( Other Identifier: Loxo Inc. )
First Posted: April 25, 2014    Key Record Dates
Last Update Posted: May 6, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
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.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bayer:
Advanced solid tumors
Neurotrophic tyrosine receptor kinase (NTRK)
NTRK1
NTRK2
NTRK3
Fusion Positive
TRK fusion
TRKA
TRKB
TRKC
ETV6