Study to Learn More About the Safety and Effectiveness of the Drug VITRAKVI During Routine Use in Patients With TRK Fusion Cancer Which is Locally Advanced or Spread From the Place Where it Started to Other Places in the Body

Official title

PrOspective Non-interventional Study in Patients With Locally Advanced or Metastatic TRK Fusion Cancer Treated With Larotrectinib

Overview

In this observational study researcher want to learn more about the effectiveness of drug VITRAKVI (generic name: larotrectinib) and how well the drug is tolerated during routine use in patients with TRK fusion cancer which is locally advanced or spread from the place where it started to other places in the body. TRK fusion cancer is a term used to describe a variety of common and rare cancers that are caused by a change to the NTRK (Neurotrophic Tyrosine Kinase) gene called a fusion. During this fusion, an NTRK gene joins together, or fuses, with a different gene. This joining results in the activation of certain proteins (TRK fusion proteins), which can cause cancer cells to multiply and form a tumor. VITRAKVI is an approved drug that blocks the action of the NTRK gene fusion. This study will enroll adult and paediatric patients suffering from a solid tumor with NTRK gene fusion for whom the decision to treat their disease with VITRAKVI has been made by their treating physicians. During the study, patients' medical information such as treatment information with VITRAKVI, other medication or treatments, changes in disease status and other health signs and symptoms will be collected within the normal medical care by the treating doctor. Participants will be observed over a period from 24 to 60 months.

Interventions

• Drug larotrectinib(Vitrakvi, BAY2757556)
  In the study, patients treated under local standard of care clinical practice; all decisions in terms of diagnostic procedures, treatments, management of the disease, and resource utilization are fully dependent on mutual agreement between the patient and the attending physician, without interference by the study initiator or study protocol

Primary outcome measures

• Number of participants with treatment-emergent adverse events (TEAEs) [Time frame: Up to 30 days after last dose]
• Severity of TEAEs [Time frame: Up to 30 days after last dose]
• Seriousness of TEAEs [Time frame: Up to 30 days after last dose]
• Reasonable causal relationship between larotrectinib and an AE [Time frame: Up to 30 days after last dose]
• Causality of TEAEs [Time frame: Up to 30 days after last dose]
• Action taken related to larotrectinib treatment [Time frame: Up to 30 days after last dose]

Secondary outcome measures (12)

• Objective response rate (ORR) [Time frame: Up to 8 years]
• Disease control rate (DCR) [Time frame: Up to 8 years]
• Duration of response (DOR) [Time frame: Up to 8 years]
• Time to response (TTR) [Time frame: Up to 8 years]
• Progression-free survival (PFS) [Time frame: Up to 8 years]
• Overall survival (OS) [Time frame: Up to 8 years]
• Total dose [Time frame: Up to 8 years]
• Starting and ending dose [Time frame: Up to 8 years]
• Dose modification during treatment [Time frame: Up to 8 years]
• Duration of treatment (DOT) [Time frame: Up to 8 years]
• ORR by patient subgroup(s) [Time frame: Up to 8 years]
• DCR by patient subgroup(s) [Time frame: Up to 8 years]

Eligibility criteria

Inclusion criteria

• Adult and pediatric (from birth to 18-year-old) patients
• 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.
• Life expectancy of at least 3 months based on clinical judgement
• Decision to treat with larotrectinib made by the treating physician prior to study enrollment
• Patients can also be enrolled if the initial visit (larotrectinib start date) occurred within 2 months ±3 days prior to informed consent signed date
• Signed informed consent form
• For patients under legal age, signed assent by the patient (where applicable) and parental/legal guardian signed informed consent is required

Exclusion criteria

• Any contraindications as listed in the local approved product information
• Pregnancy
• Participation in an investigational program with interventions outside of routine clinical practice
• Prior treatment with larotrectinib or other kinase inhibitor with TRK inhibition
• Patients with NTRK gene amplification or NTRK point mutation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 51 centers

• Banner Desert Medical Center — Mesa
• California Research Inst. — Los Angeles
• USC / Norris Comprehensive Cancer Center — Los Angeles
• UCLA - Mattel Children's Hospital — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• UCSF Benioff Children's Hospital Oakland — Oakland
• Stanford Univ Med Ctr. / Lucile Packard Children's Hosp — Palo Alto
• Providence Health System - Southern California — Santa Monica
• … and 43 more centers

Argentina · 1 center

• Many Locations — Multiple Locations

Australia · 1 center

• Many Locations — Multiple Locations

Austria · 1 center

• Many Locations — Multiple Locations

Belgium · 1 center

• Many Locations — Multiple Locations

Brazil · 1 center

• Many Locations — Multiple Locations

Canada · 1 center

• Many Locations — Multiple Locations

China · 1 center

• Many Locations — Multiple Locations

Denmark · 1 center

• Many Locations — Multiple Locations

Finland · 1 center

• Many Locations — Multiple Locations

France · 1 center

• Many Locations — Multiple Locations

Germany · 1 center

• Many Locations — Multiple Locations

Greece · 1 center

• Many Locations — Multiple Locations

Ireland · 1 center

• Many Locations — Multiple Locations

Italy · 1 center

• Many Locations — Multiple Locations

Japan · 1 center

• Many Locations — Multiple Locations

Luxembourg · 1 center

• Many Locations — Multiple Locations

Norway · 1 center

• Many Locations — Multiple Locations

Russia · 1 center

• Many Locations — Multiple Locations

Singapore · 1 center

• Many Locations — Multiple Locations

South Korea · 1 center

• Many Locations — Multiple Locations

Spain · 1 center

• Many Locations — Multiple Locations

Sweden · 1 center

• Many Locations — Multiple Locations

Switzerland · 1 center

• Many Locations — Multiple Locations

Taiwan · 1 center

• Many Locations — Multiple Locations

United Kingdom · 1 center

• Many Locations — Multiple Locations

Publications

• Yang JCH, Brose MS, Castro G, Kim ES, Lassen UN, Leyvraz S, Pappo A, Lopez-Rios F, Reeves JA, Fellous M, Penault-Llorca F, Rudzinski ER, Tabatabai G, Vassal G, Drilon A, Trent J. Rationale and design of ON-TRK: a novel prospective non-interventional study in patients with TRK fusion cancer treated with larotrectinib. BMC Cancer. 2022 Jun 7;22(1):625. doi: 10.1186/s12885-022-09687-x. PMID 35672677

Identifiers

NCT: NCT04142437 · 20324

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗