Clinical trial NCT04142437: 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2019-10-29
Enrollment: 150
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult and pediatric (from birth to 18-year-old) patients with a locally advanced or metastatic solid tumor harboring an NTRK gene fusion (detected by NGS (Next-Generation Sequencing), FISH (Fluorescent In Situ Hybridization), rt-PCR (Reverse Transcription Polymerase Chain Reaction) or other genomic testing able to detect NTRK gene fusion) assessed locally for whom a decision to treat with larotrectinib has been made before enrollment

Brief summary: 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.


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

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs)
timeFrame: Up to 30 days after last dose
measure: Severity of TEAEs
timeFrame: Up to 30 days after last dose
measure: Seriousness of TEAEs
timeFrame: Up to 30 days after last dose
measure: Reasonable causal relationship between larotrectinib and an AE
timeFrame: Up to 30 days after last dose
measure: Causality of TEAEs
timeFrame: Up to 30 days after last dose
measure: Action taken related to larotrectinib treatment
timeFrame: Up to 30 days after last dose
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 8 years
measure: Disease control rate (DCR)
timeFrame: Up to 8 years
measure: Duration of response (DOR)
timeFrame: Up to 8 years
measure: Time to response (TTR)
timeFrame: Up to 8 years
measure: Progression-free survival (PFS)
timeFrame: Up to 8 years
measure: Overall survival (OS)
timeFrame: Up to 8 years
measure: Total dose
timeFrame: Up to 8 years
measure: Starting and ending dose
timeFrame: Up to 8 years
measure: Dose modification during treatment
timeFrame: Up to 8 years
measure: Duration of treatment (DOT)
timeFrame: Up to 8 years
measure: ORR by patient subgroup(s)
timeFrame: Up to 8 years
measure: DCR by patient subgroup(s)
timeFrame: Up to 8 years
measure: DOR by patient subgroup(s)
timeFrame: Up to 8 years
measure: TTR by patient subgroup(s)
timeFrame: Up to 8 years
measure: PFS by patient subgroup(s)
timeFrame: Up to 8 years
measure: OS by patient subgroup(s)
timeFrame: Up to 8 years
measure: Number of patients with change in height and weight from baseline by visit, neurological abnormalities (normal/abnormal)
timeFrame: Up to 8 years
measure: Number of patients with abnormal developmental milestones
timeFrame: Up to 8 years
measure: Number of patients with abnormal Tanner stage
timeFrame: Up to 8 years
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Banner Desert Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: California Research Inst.
state: California
city: Los Angeles
country: United States
facility: USC / Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: UCLA - Mattel Children's Hospital
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: Palo Alto
country: United States
facility: Stanford Univ Med Ctr. / Lucile Packard Children's Hosp
state: California
city: Santa Monica
country: United States
facility: Providence Health System - Southern California
state: California
city: Torrance
country: United States
facility: Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
state: California
city: Grand Junction
country: United States
facility: SCL Health
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Nemours Children's Hospital
state: Florida
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology Hematology
state: Indiana
city: Terre Haute
country: United States
facility: Regional Health Hope Center
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: South Portland
country: United States
facility: Maine Health
state: Maine
city: Baltimore
country: United States
facility: Univ. of Maryland / Greenebaum Comp. Cancer Ctr.
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins / Sidney Kimmel Cancer Center
state: Maryland
city: Frederick
country: United States
facility: Frederick Health-James M Stockman Cancer Institute
state: Maryland
city: Boston
country: United States
facility: Tufts / Neely Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's / Dana Farber
state: Massachusetts
city: Farmington Hills
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Lansing
country: United States
facility: Sparrow Cancer Center
state: Michigan
city: Las Vegas
country: United States
facility: Nevada Cancer Research Foundation
state: Nevada
city: Morristown
country: United States
facility: Atlantic Hem Onc / Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Buffalo
country: United States
facility: Great Lakes Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Children's Cancer Center
state: New York
city: Staten Island
country: United States
facility: Staten Island Univ. Hospital (Northwell Health)
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University / Vidant Health
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Comp. Cancer Ctr. / James Cancer Hospital
state: Ohio
city: Youngstown
country: United States
facility: Mercy Health Youngstown
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania (Penn Med)
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny Health Network
state: Pennsylvania
city: Charleston
country: United States
facility: Medical Univ. of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center / Children's Health
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Murray
country: United States
facility: Intermountain Healthcare - Intermountain Medical Center
state: Utah
city: Saint George
country: United States
facility: Intermountain Healthcare - Dixie Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: Univ. of Utah / Huntsman Cancer Center
state: Utah
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: La Crosse
country: United States
facility: Gundersen Health System
state: Wisconsin
city: Madison
country: United States
facility: SSM Health Cancer Center - Dean Medical Group
state: Wisconsin
city: Multiple Locations
country: Argentina
facility: Many Locations
city: Multiple Locations
country: Australia
facility: Many Locations
city: Multiple Locations
country: Austria
facility: Many Locations
city: Multiple Locations
country: Belgium
facility: Many Locations
city: Multiple Locations
country: Brazil
facility: Many Locations
city: Multiple Locations
country: Canada
facility: Many Locations
city: Multiple Locations
country: China
facility: Many Locations
city: Multiple Locations
country: Denmark
facility: Many Locations
city: Multiple Locations
country: Finland
facility: Many Locations
city: Multiple Locations
country: France
facility: Many Locations
city: Multiple Locations
country: Germany
facility: Many Locations
city: Multiple Locations
country: Greece
facility: Many Locations
city: Multiple Locations
country: Ireland
facility: Many Locations
city: Multiple Locations
country: Italy
facility: Many Locations
city: Multiple Locations
country: Japan
facility: Many Locations
city: Multiple Locations
country: Korea, Republic of
facility: Many Locations
city: Multiple Locations
country: Luxembourg
facility: Many Locations
city: Multiple Locations
country: Norway
facility: Many Locations
city: Multiple Locations
country: Russian Federation
facility: Many Locations
city: Multiple Locations
country: Singapore
facility: Many Locations
city: Multiple Locations
country: Spain
facility: Many Locations
city: Multiple Locations
country: Sweden
facility: Many Locations
city: Multiple Locations
country: Switzerland
facility: Many Locations
city: Multiple Locations
country: Taiwan
facility: Many Locations
city: Multiple Locations
country: United Kingdom
facility: Many Locations
Study officials:
References:
citation: 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.