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 (ON-TRK)

• ClinicalTrials.gov Identifier: NCT04142437
• Recruitment Status: Recruiting
• First Posted: October 29, 2019
• Last Update Posted: December 5, 2022
• Sponsor: Bayer
• Information provided by (Responsible Party): Bayer

Tracking Information

• First Submitted Date: October 17, 2019
• First Posted Date: October 29, 2019
• Last Update Posted Date: December 5, 2022
• Actual Study Start Date: April 3, 2020
• Estimated Primary Completion Date: November 30, 2029 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 25, 2019)

• 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 ]
• Outcome of TEAEs [ 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 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 12, 2021)

• 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 ]
• DOR by patient subgroup(s) [ Time Frame: Up to 8 years ]
• TTR by patient subgroup(s) [ Time Frame: Up to 8 years ]
• PFS by patient subgroup(s) [ Time Frame: Up to 8 years ]
• OS by patient subgroup(s) [ Time Frame: Up to 8 years ]
• Number of patients with abnormal neurological assessments [ Time Frame: Up to 8 years ]
• Change in height and weight from baseline by visit [ Time Frame: Up to 8 years ]
  Pediatric cohort only
• Number of patients with abnormal developmental milestones [ Time Frame: Up to 8 years ]
  Pediatric cohort only
• Number of patients with abnormal Tanner stage [ Time Frame: Up to 8 years ]
  Pediatric cohort only

Original Secondary Outcome Measures (submitted: October 25, 2019)

• 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 ]
• DOR by patient subgroup(s) [ Time Frame: Up to 8 years ]
• TTR by patient subgroup(s) [ Time Frame: Up to 8 years ]
• PFS by patient subgroup(s) [ Time Frame: Up to 8 years ]
• OS by patient subgroup(s) [ Time Frame: Up to 8 years ]
• Change in height and weight from baseline by visit [ Time Frame: Up to 8 years ]
  Pediatric cohort only
• Number of patients with abnormal neurological assessments [ Time Frame: Up to 8 years ]
  Pediatric cohort only
• Number of patients with abnormal developmental milestones [ Time Frame: Up to 8 years ]
  Pediatric cohort only
• Number of patients with abnormal Tanner stage [ Time Frame: Up to 8 years ]
  Pediatric cohort only

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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 by the treating physician prior to or at the time of study enrollment
• Condition: Locally Advanced or Metastatic Solid Tumor Harboring an NTRK Gene Fusion

Intervention

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

Study Groups/Cohorts

• GI
  adult patients with gastrointestinal (GI) cancer
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• H&N
  adult patients with head and neck (H&N) cancer
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• STS
  adult patients with soft tissue sarcoma (STS)
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• CNS
  adult patients with primary central nervous system (CNS) cancer
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• Lung
  adult patients with lung cancer
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• Melanoma
  adult patients with melanoma
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• Pediatric
  all pediatric patients regardless of tumor type will be enrolled under this cohort
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)
• other
  patients with other tumor types
  Intervention: Drug: larotrectinib(Vitrakvi, BAY2757556)

• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 25, 2019): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 31, 2030
• Estimated Primary Completion Date: November 30, 2029 (Final data collection date for primary outcome measure)

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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No

Contacts

Contact: Bayer Clinical Trials Contact; (+)1-888-84 22937; clinical-trials-contact@bayer.com

• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Japan, Korea, Republic of, Luxembourg, Norway, Russian Federation, Singapore, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04142437
• Other Study ID Numbers: 20324
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

• Current Responsible Party: Bayer
• Original Responsible Party: Same as current
• Current Study Sponsor: Bayer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bayer
• Verification Date: November 2022