check_circleStudy Completed

Solid tumors harboring NTRK fusion

A study to test the safety of the investigational drug selitrectinib in children and adults that may treat cancer

Trial purpose

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.

Key Participants Requirements

Sex

All

Age

1 - N/A
  • - 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
  • - 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.

Trial summary

Enrollment Goal
81
Trial Dates
July 2017 - January 2023
Phase
Phase 1
Could I Receive a placebo
No
Products
selitrectinib (LOXO-195, BAY2731954)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
Stanford Cancer CenterPalo Alto, 94304, United States
Completed
Massachusetts General HospitalBoston, 02114-2696, United States
Completed
Oregon Health and Science UniversityPortland, 97239, United States
Completed
UCLA Jonsson Comprehensive Cancer CenterLos Angeles, 90095-1781, United States
Completed
Dana-Farber Cancer InstituteBoston, 02215, United States
Completed
St. Jude Children's Research HospitalMemphis, 38105, United States
Withdrawn
University of Texas Southwestern Medical CenterDallas, 75390, United States
Completed
University of MichiganAnn Arbor, 48109, United States
Completed
Children's Hospital of PhiladelphiaPhiladelphia, 19104, United States
Completed
Seattle Children's HospitalSeattle, 98105, United States
Completed
Sarah Cannon Research InstituteNashville, 37203, United States
Withdrawn
University of Texas Southwestern Medical CenterDallas, 75390, United States
Completed
Virginia Oncology AssociatesNorfolk, 23502, United States
Completed
Univ.of California-San Diego Moores Cancer CenterLa Jolla, 92093, United States
Withdrawn
Ochsner Medical Center - New OrleansNew Orleans, 70121, United States
Completed
Midwestern Regional Medical CenterZion, 60099, United States
Withdrawn
Eastern Regional Medical CenterPhiladelphia, 19124, United States
Withdrawn
Sarah Cannon Research Institute at HealthONEDenver, 80218, United States
Withdrawn
University of Utah - OncologySalt Lake City, 84112, United States
Completed
Fondazione IRCCS Istituto Nazionale dei TumoriMilano, 20133, Italy
Completed
Institut Curie - Ulm - ParisPARIS cedex 5, 75248, France
Completed
Institut Gustave Roussy - Département de Médecine OncologiqueVILLEJUIF CEDEX, 94805, France
Completed
Rigshospitalet - KræftbehandlingCopenhagen, 2100, Denmark
Completed
Universitätsklinikum HeidelbergHeidelberg, 69115, Germany
Withdrawn
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Completed
Fundacion Jimenez Diaz (Clinica de la Concepcion)Madrid, 28040, Spain
Withdrawn
Austin HealthHeidelberg, 3084, Australia
Withdrawn
Sarah Cannon Research Institute UK LtdLondon, W1G 6AD, United Kingdom
Completed
Sydney Children’s HospitalSydney, 2031, Australia
Withdrawn
Seoul National University HospitalSeoul, 3080, Korea,_republic_of
Completed
National Cancer Center SingaporeSingapore, 168583, Singapore
Withdrawn
Prince of Wales HospitalHong Kong, MISSING, Hong Kong
Completed
Avera Cancer InstituteSioux Falls, 57105, United States
Withdrawn
CHU Sainte-JustineMontreal, H3T 1C5, Canada
Completed
UZ AntwerpenEDEGEM, 2650, Belgium
Completed
Tallaght HospitalDublin, D24NR0A, Ireland
Withdrawn
McGill University Health CenterMontreal, H3A 2B4, Canada
Withdrawn
KK Women's and Children's HospitalSingapore, 229899, Singapore
Completed
Children's Healthcare of AtlantaAtlanta, 30322, United States
Withdrawn
Beijing Cancer HospitalBeijing, 100142, China
Withdrawn
Zhongshan Hospital, Fudan UniversityShanghai, 200032, China
Withdrawn
Zhejiang Cancer HospitalHangzhou, 310022, China
Withdrawn
West China Hospital Sichuan UniversityChengdu, 610041, China
Completed
Royal Children's Hospital MelbourneParkville, 3052, Australia
Withdrawn
Charité Comprehensive Cancer Center (CCCC)Berlin, 12203, Germany
Withdrawn
Duke University Medical CenterDurham, 27710, United States
Withdrawn
University of Wisconsin - MadisonMadison, 53792, United States
Withdrawn
University Hospitals Cleveland Medical CenterCleveland, 44106, United States
Withdrawn
Levine Cancer InstituteCharlotte, 28204-2990, United States
Withdrawn
UCSF Med Center Helen Diller Family Comp Cancer CenterSan Francisco, 94158, United States
Withdrawn
Institut Bergonié - Unicancer Nouvelle AquitaineBORDEAUX CEDEX, 33076, France
Withdrawn
Sunnybrook Health Sciences CentreToronto, M4N 3M5, Canada
Withdrawn
Christie HospitalManchester, M20 4BX, United Kingdom
Withdrawn
Hong Kong United Oncology CentreKowloon, Hong Kong
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States

Primary Outcome

  • Maximum tolerated dose (MTD)
    date_rangeTime Frame:
    Up to 42 days
  • Recommended dose
    date_rangeTime Frame:
    Up to 12 months

Secondary Outcome

  • Incidence of adverse events
    date_rangeTime Frame:
    Up to 56 months
  • Severity of adverse events
    Severity is assessed using CTCAE version 4.03
    date_rangeTime Frame:
    Up to 56 months
  • Duration of adverse events
    date_rangeTime Frame:
    Up to 56 months
  • Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
    date_rangeTime Frame:
    Up to 56 months
  • Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
    date_rangeTime Frame:
    Up to 56 months
  • 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.
    date_rangeTime Frame:
    Up to 56 months
  • 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.
    date_rangeTime Frame:
    Up to 56 months
  • Maximum concentration (Cmax) of BAY2731954 in plasma
    date_rangeTime Frame:
    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)
  • 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)
    date_rangeTime Frame:
    At defined time points for different cohort, up to 10 hours post-dose

Trial design

A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Non-randomized
Blinding
N/A
Assignment
Sequential Assignment
Trial Arms
2