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A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03215511
Recruitment Status : Completed
First Posted : July 12, 2017
Last Update Posted : March 26, 2024
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Harboring NTRK Fusion Drug: Selitrectinib (BAY2731954) Phase 1

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 81 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the TRK Inhibitor Selitrectinib (BAY 2731954) in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers
Actual Study Start Date : July 3, 2017
Actual Primary Completion Date : April 11, 2022
Actual Study Completion Date : January 30, 2023

Arm Intervention/treatment
Experimental: Cancer participants <12 years
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.
Drug: Selitrectinib (BAY2731954)
Selitrectinib is administered as capsules or liquid formulation.
Other Name: Loxo-195

Experimental: Cancer participants ≥12 years
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).
Drug: Selitrectinib (BAY2731954)
Selitrectinib is administered as capsules or liquid formulation.
Other Name: Loxo-195

Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: Up to 42 days ]
  2. Recommended dose [ Time Frame: Up to 12 months ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 56 months ]
  2. Severity of adverse events [ Time Frame: Up to 56 months ]
    Severity is assessed using CTCAE version 4.03

  3. Duration of adverse events [ Time Frame: Up to 56 months ]
  4. Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 56 months ]
  5. Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 56 months ]
  6. Overall response rate (ORR) in subjects with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator [ Time Frame: Up to 56 months ]
    ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

  7. Overall response rate (ORR) in subjects with primary central nervous system (CNS) malignancies determined by investigator [ Time Frame: Up to 56 months ]
    ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.

  8. Maximum concentration (Cmax) of BAY2731954 in plasma [ Time Frame: 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) ]
  9. 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) [ Time Frame: At defined time points for different cohort, up to 10 hours post-dose ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Month and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Advanced solid tumor for which, in the opinion of the investigator, no other standard therapy offers greater benefit.
  • 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
  • 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.
  • 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).
  • Life expectancy of at least 3 months.
  • Adequate hematologic, hepatic and renal function.
  • 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.
  • Ability to receive study drug orally or by enteral administration

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03215511

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Sponsors and Collaborators
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Bayer Identifier: NCT03215511    
Other Study ID Numbers: 20810
LOXO-EXT-17005 ( Other Identifier: Loxo Oncology, Inc. )
2017-004246-20 ( EudraCT Number )
First Posted: July 12, 2017    Key Record Dates
Last Update Posted: March 26, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
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 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 member section of the portal.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Solid Tumor
Metastatic cancer
Advanced cancer
Neurotrophic tyrosine receptor kinase (NTRK)
Fusion Positive
Additional relevant MeSH terms:
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Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action