Oral TRK Inhibitor LOXO-101 for Treatment of Advanced Adult Solid Tumors

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. Identifier: NCT02122913
Recruitment Status : Recruiting
First Posted : April 25, 2014
Last Update Posted : December 6, 2017
Information provided by (Responsible Party):
Loxo Oncology, Inc.

Brief Summary:
This is a multicenter, open-label, Phase 1 study of orally administered larotrectinib in adult subjects with advanced solid tumors and a NTRK1, NTRK2, or NTRK3 gene fusion that have progressed or are non responsive to available therapies and for which no standard or available curative therapy exists.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Drug: Larotrectinib 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. This will be followed by an expansion phase in solid tumor subjects with an NTRK fusion. During the escalation phase, larotrectinib will be taken once daily (QD) or twice daily (BID). During the expansion phase, the larotrectinib dose selected from the escalation phase will be explored in approximately 40 additional subjects. Enrollment into the dose esclation portion of this study has been completed and is currently closed to enrollment. Patients will continue to be considered for enrollment into the dose expansion portion of this study.

The objectives of the dose escalation phase are to determine the safety, tolerability, pharmacokinetic profile, and recommended dose of orally administered larotrectinib. The objectives of the expansion phase are to better characterize the safety and efficacy of larotrectinib in patients with NTRK fusions.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Single Group 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 : May 2014
Actual Primary Completion Date : February 2017
Estimated Study Completion Date : April 2019

Arm Intervention/treatment
Experimental: Larotrectinib
  • Escalation- Multiple doses of larotrectinib.
  • Expansion- The MTD dose and/or the appropriate dose for furher clinical investigation of larotrectinib found during the Escalation Phase.
Drug: Larotrectinib
Oral larotrectinib
Other Name: LOXO-101

Primary Outcome Measures :
  1. The maximum tolerated dose (MTD) and/or the appropriate dose for further clinical investigation.[Escalation] [ Time Frame: 32 months [Actual] ]
  2. Safety [ Time Frame: 19 months [Estimated] ]
    Assessed by clinical review of all relevant parameters including AEs, SAEs, laboratory values, virals signs, ECG results, concomitant medications and thyroid function.

Secondary Outcome Measures :
  1. Pharmacokinetic parameters of LOXO-101 including Cmax, Tmax, t1/2, and AUC following both QD and BID dosing. [ Time Frame: 19 months [Estimated] ]
  2. Overall Response Rate [ Time Frame: Up to 60 months ]
    As assessed using RECIST 1.1 or RANO, as appropriate, per tumor type

  3. Duration of Response [ Time Frame: Up to 60 months ]

Information from the National Library of Medicine

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

Escalation Phase [Inclusion]

  • Locally advanced or metastatic adult 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;
  • ECOG score of 0, 1 or 2;
  • Adequate hematologic, hepatic, and renal function;

Expansion Phase [Inclusion]

  • Escalation Phase inclusion criteria
  • Evidence of the NTRK fusion as previously determined with prior testing from a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent certified laboratory.

Exclusion (for both Escalation and Expansion)

• Current treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor or inducer (EIAEDs and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed)

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 identifier (NCT number): NCT02122913

Contact: Patient Advocacy 1-855-NTRK-123

United States, Colorado
University of Colorado Cancer Center Recruiting
Aurora, Colorado, United States, 80045
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
United States, Ohio
University Hospitals of Cleveland Recruiting
Cleveland, Ohio, United States, 11100
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh Medical Center Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Loxo Oncology, Inc.
Study Director: Michael Cox, PharmD, , MHSc, BCOP Loxo Oncology

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Loxo Oncology, Inc. Identifier: NCT02122913     History of Changes
Other Study ID Numbers: LOXO-TRK-14001
First Posted: April 25, 2014    Key Record Dates
Last Update Posted: December 6, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Loxo Oncology, Inc.:
NTRK fusion positive
NTRK gene rearrangements
NTRK1 fusion
NTRK2 fusion
NTRK3 fusion
NTRK1 gene rearrangement
NTRK2 gene rearrangement
NTRK3 gene rearrangement
solid tumors
CNS tumors
central nervous system tumors
TRK fusion
ETV6 fusion
ETV6 gene rearrangement
solid CNS tumor
Advanced CNS tumor
Primary CNS tumor
Metastatic CNS tumor