THE ON-TRK STUDY
PrOspective Non-interventional study in patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib (Vitrakvi®)
Enrolment goal
Data will be collected from up to 150 patients with NTRK gene fusion globally
Trial dates
Enrolment April 2020 to Dec 2024
Overall study duration April 2020 to March 2030
Phase 4
NCT04142437
Product
Larotrectinib (Vitrakvi®) BAY2757556
Successful global investigator pediatric-focused meeting
The ON-TRK global investigator meeting, with a focus on the pediatric patients, was conducted successfully on 26th January 2024. This event brought together investigators from China, United States, Germany, Argentina, and the ON-TRK global study team. While some attendees joined in person in Beijing, others participated online.
The meeting received an overwhelmingly positive response. Dr. Domnita-Ileana Burcoveanu, medical expert and study lead, kicked off the meeting by introducing all investigators. Geoffrey Wyckaert, study manager, provided a brief overview of the study's current status. Dr. Carlos Carrasco, safety lead, shared crucial safety topics identified by ON-TRK pediatric investigators, fostering an environment of open dialogue and collaboration.
This global investigator meeting showcased a remarkable dynamic between experts from various countries, fostering an environment of collaboration and knowledge sharing. The meeting proved to be fruitful, with engaging discussions and valuable insights exchanged among the participants.
The study team is optimistic that the positive outcomes of this meeting will significantly impact the conduct of the study, particularly in patient enrollment.
With the enrollment completion foreseen by end of 2024, the collaborative spirit and shared expertise from this meeting are expected to contribute to the successful progression of the study, ultimately benefiting patients and advancing medical research.
Background
Tropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide variety of tumors. Larotrectinib (Vitrakvi®) is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib (Vitrakvi®) was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. (LOXO-TRK-14001 (NCT02122913), NAVIGATE (NCT02576431) and SCOUT (NCT02637687)).
"The ON-TRK study is crucial to generating further safety data in a real-life setting, and to addressing post-approval commitments."
Silvia Novello, Professor of Medical Oncology, University of Turin, Italy, and President of WALCE (Women Against Lung Cancer Europe)
Trial Design and Purpose
ON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study. This observational study aims to describe and help better understanding for safety and effectiveness of larotrectinib (Vitrakvi®) in real-world practice conditions.
The effectiveness of larotrectinib (Vitrakvi®) in the overall study population as well as in patient subgroups will also be evaluated. Larotrectinib (Vitrakvi®) treatment patterns in real-world practice, including dosing and duration of treatment, will be described. During the study, all patient medical information such as Larotrectinib (Vitrakvi®) treatment, co morbidities, other treatments etc. will be collected within the medical file at the investigating sites. ON-TRK is currently running and enrolling globally.
Enrolment status
Enrolment status by country and region.
Observational Real-World Data
The importance of observational real-world data is escalating in the era of Precision Oncology, so medical community is strongly investing time and resources into implementing characterizing and interpreting of biomarkers predictive of response to treatment with targeted drugs, as well as into gathering RWD of patient efficacy and safety data. The continued growth of ON-TRK is important, not only for patients with TRK fusion cancer, but also for all with a vision for a future of personalised cancer care.
Inclusion and Exclusion criteria
Setting the parameters that guide selection and exclusion
A broad cohort
International, prospective, open-label, multi-center, multi-cohort, non-interventional study.
Adult patients within different tumor type cohorts will be followed for at least two years.
Patients < 18 years old will be enrolled under a ‘pediatric’ cohort regardless of tumor type and will be followed for 5 years to evaluate the risk of potential long-term effects of larotrectinib on their growth and neurological development. Specific cohorts: adults with gastrointestinal (GI), head and neck (H&N), lung, soft tissue sarcoma (STS), primary central nervous system (CNS), all pediatric patients regardless of tumor type will be enrolled under this cohort; other patients with other tumor types.
Inclusion
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Adult and pediatric (from birth to 18 years old) patients
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Patients with locally advanced or metastatic solid tumor harboring an NTRK gene fusion. NTRK (NTRK1, NTRK2, and NTRK3) gene fusions will be identified locally. Acceptable methods of detection of NTRK gene fusion include NGS, fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction (rt-PCR) or any other genomic testing able to detect NTRK gene fusion. If a pan-TRK IHC method is used, this result needs to be accompanied with the results using one of the other methods noted above.
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Life expectancy of at least 3 months based on clinical judgement
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Decision to treat with larotrectinib (Vitrakvi®) made by the treating physician prior to study enrollment
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Patients can also be enrolled if the initial visit (larotrectinib (Vitrakvi®) start date) occurred within 2 months ±3 days prior to informed consent signed date
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Signed informed consent form
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For patients under legal age, signed assent by the patient (where applicable) and parental/legal guardian signed informed consent is required
Exclusion
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Any contraindications as listed in the local approved product information
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Pregnancy
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Participation in an investigational program with interventions outside of routine clinical practice
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Prior treatment with larotrectinib (Vitrakvi®) or other kinase inhibitor with TRK inhibition
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Patients with NTRK gene amplification or NTRK point mutation
Steering Committee
Members
Dr. Theodore Laetsch,
UT Southwestern Medical Center / Children’s Health, Philadelphia, USA
Dr. Silvia Novello,
AOU S. Luigi Gonzaga di Orbassano, Turin, Italy
Dr. Jonathan Trent,
Retreat Hospital, Miami, USA
Dr. Ghazaleh Tabatabai,
Interdisciplinary Division of Neuro-Oncology, Tübingen, Germany
ON-TRK faces
The neuro-oncology department at Buenos Aires' FLENI Institute sets the standard for brain, spinal, and peripheral nervous system tumor care in the region. With cutting-edge technology, an experienced interdisciplinary team, and patient-centered values, we deliver unmatched individualized treatment.
The medical team is spearheaded by Dr. Blanca Diez, a neuro-oncologist with a career spanning over four decades. She is supported by two oncologists dedicated to pediatric patients and four others specializing in adult care, all of whom have received training from nationally and internationally recognized centers of excellence. For each case, we complement their expertise with input across specialties – neurosurgery, radiation oncology, palliative care, pathology and more.
Our dedication to patients reaches beyond the clinical practice. An energetic clinical research program, directed by Dr. Agustin Cardoso and staffed across medical roles, drives the development of pioneering treatments. By participating in clinical trials alongside esteemed global centers, we are progressing science.
We have recently joined the ON-TRK study as a participating center, aligning our expertise with all the other prestigious international sites. We have proudly recruited the first Argentinian patient for this study, a 9-year-old girl with a low-grade glioma and NTRK gene fusion and we are enthusiastically continuing our efforts to enlist new participants, furthering our collective fight against cancer.
At FLENI, our ambition transcends merely treating cancer; we are dedicated to forging new pathways of hope.
Resource library
Informative ON-TRK resources to support you
Contact for ON-TRK sites
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