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

Solid Tumors Harboring NTRK Fusion Clinical Trial

Official title:

A Phase 1 Study of the Oral TRK Inhibitor Larotrectinib in Adult Patients With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02122913
• Other study ID #: 20288
• Secondary ID: LOXO-TRK-14001
• Status: Completed
• Phase: Phase 1
• Start date: May 4, 2014
• Est. completion date: April 9, 2021

Study information

• Verified date: November 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: April 9, 2021
• Est. primary completion date: February 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Solid Tumors Harboring NTRK Fusion

Intervention

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

Locations

Country	Name	City	State
United States	University of Colorado	Aurora	Colorado
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

References & Publications (1)

Waguespack SG, Drilon A, Lin JJ, Brose MS, McDermott R, Almubarak M, Bauman J, Casanova M, Krishnamurthy A, Kummar S, Leyvraz S, Oh DY, Park K, Sohal D, Sherman E, Norenberg R, Silvertown JD, Brega N, Hong DS, Cabanillas ME. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. Eur J Endocrinol. 2022 Apr 29;186(6):631-643. doi: 10.1530/EJE-21-1259. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events		25 months
Primary	Severity of adverse events	The severity of adverse events will be assesssed according to the NCI CTCAE version 4.03.	25 months
Primary	Maximum tolerated dose (MTD)		25 months
Primary	Recommended dose for dose expansion		25 months
Secondary	Maximum concentration of larotrectinib in plasma (Cmax)		Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Secondary	Time to maximum concentration of larotrectinib in plasma (Tmax)		Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Secondary	Half-life of larotrectinib in plasma (t1/2)		Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Secondary	Area under the concentration versus time curve of larotrectinib in plasma (AUC)		Predose and 0.25, 0.5, 1, 2, 4, 6 and 8 hours after drug administration on Days 1 and 8 of Cycle 1
Secondary	Overall Response Rate (ORR)	Assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or Response Assessment in Neuro-Oncology (RANO) as appropriate	Up to 60 months
Secondary	Duration of Response (DOR)		Up to 60 months