A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer
- Conditions
- Solid Tumors Harboring NTRK Fusion
- Interventions
- Registration Number
- NCT03215511
- Lead Sponsor
- Bayer
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 81
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Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
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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
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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.
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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).
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Life expectancy of at least 3 months.
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Adequate hematologic, hepatic and renal function.
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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.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Cancer participants ≥12 years Selitrectinib (BAY2731954) A 3+3 dose escalation design will be used to determine the maximum tolerated dose (MTD)/recommended dose for further study, enrolling 3 to 6 participants per cohort with a starting dose level of 100 mg twice daily (BID). Cancer participants <12 years Selitrectinib (BAY2731954) A Rolling-6 dose escalation design will be used. The starting dose for participants age \< 12 years will be 25% below the highest dose level cohort divided by 1.73 m\^2 cleared by the Safety Review Committee (SRC) for subjects age 12 years and older.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) Up to 42 days Recommended dose Up to 12 months
- Secondary Outcome Measures
Name Time Method Incidence of adverse events Up to 56 months Severity of adverse events Up to 56 months Severity is assessed using CTCAE version 4.03
Duration of adverse events Up to 56 months Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration Up to 56 months Severity of safety-relevant changes in clinical parameters or vital signs after drug administration Up to 56 months Overall response rate (ORR) in subjects with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator Up to 56 months ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Overall response rate (ORR) in subjects with primary central nervous system (CNS) malignancies determined by investigator Up to 56 months ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.
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) 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
Trial Locations
- Locations (29)
Rigshospitalet - Kræftbehandling
🇩🇰Copenhagen, Denmark
Univ.of California-San Diego Moores Cancer Center
🇺🇸La Jolla, California, United States
UCLA Jonsson Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Stanford Cancer Center
🇺🇸Palo Alto, California, United States
Children's Healthcare of Atlanta
🇺🇸Atlanta, Georgia, United States
Midwestern Regional Medical Center
🇺🇸Zion, Illinois, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Sydney Children's Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Children's Hospital Melbourne
🇦🇺Parkville, Victoria, Australia
UZ Antwerpen
🇧🇪Edegem, Belgium
Institut Curie - Ulm - Paris
🇫🇷PARIS cedex 5, France
Institut Gustave Roussy - Département de Médecine Oncologique
🇫🇷Villejuif Cedex, France
Universitätsklinikum Heidelberg
🇩🇪Heidelberg, Baden-Württemberg, Germany
Tallaght Hospital
🇮🇪Dublin, Ireland
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Lombardia, Italy
National Cancer Center Singapore
🇸🇬Singapore, Singapore
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
🇪🇸Barcelona, Spain
Fundacion Jimenez Diaz (Clinica de la Concepcion)
🇪🇸Madrid, Spain