A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer

Solid Tumors Harboring NTRK Fusion Clinical Trial

Official title:

A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03215511
• Other study ID #: 20810
• Secondary ID: LOXO-EXT-1700520
• Status: Completed
• Phase: Phase 1
• Start date: July 3, 2017
• Est. completion date: January 30, 2023

Study information

• Verified date: March 2024
• 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 new drug selitrectinib in children and adults with cancer having a change in a particular gene (NTRK1, NTRK2 or NTRK3). The drug may treat cancer by interfering with the effect of the NTRK genes on cancer growth. The study also investigates how the drug is absorbed and processed in the human body, and how well and for how long the cancer responds to the drug. This is the first study to test selitrectinib in humans with cancer, for whom no other effective therapy exists.

Description:

The primary objective is to determine the recommended dose for further study of oral selitrectinib with previously treated neurotrophic tyrosine kinase (NTRK) cancers in 2 patient groups: a) aged 12 years and older and b) younger than 12 years. Secondary objectives of Phase I are to characterize the pharmakokinetic properties of the test drug, its safety and tolerability, and to assess the objective response rate (ORR) of NTRK-tumors.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: January 30, 2023
• Est. primary completion date: April 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month and older

Eligibility

Inclusion Criteria:

• Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
• A solid tumor diagnosis in the setting of:
• a) a documented NTRK fusion and a clinical history of relapse following a response to a prior TRK inhibitor
• b) a documented NTRK fusion unresponsive to a prior TRK inhibitor
• c) a documented NTRK fusion and a clinical history of intolerance to a prior TRK inhibitor
• NTRK gene fusions will be identified in a CLIA-certified (or equivalently-accredited diagnostic) laboratory. If such a report cannot be provided, other available certifications/accreditations are required and need to be documented. Patients with infantile fibrosarcoma (IFS) or congenital mesoblastic nephroma (CMN) may be enrolled based on an ETV6+ FISH test without identifying NTRK3.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) score = 2 in adults or Karnofsky Performance Status (KPS) Score=50% (age = 16 years) or Lansky Performance Score (LPS) = 40% (age < 16 years).
• Life expectancy of at least 3 months.
• Adequate hematologic, hepatic and renal function.
• Patients with stable central nervous system (CNS) primary tumor, brain metastases, or treated spinal cord compression are eligible if neurological symptoms have been stable for 7 days prior to the first dose of selitrectinib.
• Ability to receive study drug orally or by enteral administration

Exclusion Criteria:

• Prior exposure to second generation TRK inhibitor (e.g. selitrectinib, repotrectinib [TPX-0005]), taletrectinib [DS-6501b/AB-106]). Exception is in case patient presented intolerance to the second generation TRK inhibitor agent and the duration of exposure was less than 28 days. No previous treatment with selitrectinib is allowed.
• Concurrent treatment with a strong CYP3A4 inhibitor or inducer, consumption of grapefruit juice or Seville oranges, or drugs associated with QT prolongation.
• Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of selitrectinib, or prolongation of QT interval corrected for heart rate (QTc interval) >480 milliseconds within past 6 months
• Major surgery within 7 days of enrollment
• Uncontrolled systemic bacterial, fungal or viral infection.
• Pregnancy or lactation.
• Known hypersensitivity to selitrectinib or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.

Related Conditions & MeSH terms

• Solid Tumors Harboring NTRK Fusion

Intervention

Drug:
• Selitrectinib (BAY2731954)
Selitrectinib is administered as capsules or liquid formulation.

Locations

Country	Name	City	State
Australia	Royal Children's Hospital Melbourne	Parkville	Victoria
Australia	Sydney Children's Hospital	Sydney	New South Wales
Belgium	UZ Antwerpen	Edegem
Denmark	Finsen Centre	Copenhagen
France	Institut Curie - Ulm - Paris	Paris
France	Institut Gustave Roussy - Département de Médecine Oncologique	Villejuif
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Ireland	Tallaght Hospital	Dublin
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano	Lombardia
Singapore	National Cancer Center Singapore	Singapore
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Fundacion Jimenez Diaz (Clinica de la Concepcion)	Madrid
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Univ.of California-San Diego Moores Cancer Center	La Jolla	California
United States	UCLA Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	St. Jude Children's Research Hospital	Memphis	Tennessee
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Stanford Cancer Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Seattle Children's Hospital	Seattle	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Midwestern Regional Medical Center	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Denmark,  France,  Germany,  Ireland,  Italy,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD)		Up to 42 days
Primary	Recommended dose		Up to 12 months
Secondary	Incidence of adverse events		Up to 56 months
Secondary	Severity of adverse events	Severity is assessed using CTCAE version 4.03	Up to 56 months
Secondary	Duration of adverse events		Up to 56 months
Secondary	Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration		Up to 56 months
Secondary	Severity of safety-relevant changes in clinical parameters or vital signs after drug administration		Up to 56 months
Secondary	Overall response rate (ORR) in subjects with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator	ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Up to 56 months
Secondary	Overall response rate (ORR) in subjects with primary central nervous system (CNS) malignancies determined by investigator	ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.	Up to 56 months
Secondary	Maximum concentration (Cmax) of BAY2731954 in plasma		Predose, 0.25, 0.5, 1, 2, 4, 6, 8 hours post-dose on Day 1, predose, 0.5, 1, 2, 4 post-dose on Day 8 of Cycle 1 (cycle length 28 days)
Secondary	Area under the concentration versus time curve of BAY2731954 in plasma (AUC (0-10), AUC(0-12) for BID dosing and AUC(0-24) for QD dosing)		At defined time points for different cohort, up to 10 hours post-dose

External Links

•   Click here to find further information and, after study completion, the study results according to Bayer's transparency standards
•   Click here to find information about studies related to Bayer Healthcare products conducted in Europe.