Clinical Trials /

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

NCT03215511

Description:

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.

Related Conditions:
  • Congenital Mesoblastic Nephroma
  • Infantile Fibrosarcoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer
  • Official Title: A Phase 1/2 Study of the TRK Inhibitor Selitrectinib in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Clinical Trial IDs

  • ORG STUDY ID: 20810
  • SECONDARY ID: LOXO-EXT-17005
  • SECONDARY ID: 2017-004246-20
  • NCT ID: NCT03215511

Conditions

  • Solid Tumors Harboring NTRK Fusion

Interventions

DrugSynonymsArms
Selitrectinib (BAY2731954)Loxo-195Phase 1: Cancer patients <12 years

Purpose

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.

Detailed Description

      The trial will be conducted in 2 parts: dose escalation (Phase I ) and dose expansion (Phase
      2) .

      The primary objective of Phase 1 is to establish the recommended dose of selitrectinib to
      treat neurotrophic tyrosine kinase (NTRK) fusion cancers in patients a) aged 12 years and
      older and b) younger than 12 years. Secondary objectives of Phase 1 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.

      The primary objective of Phase 2 is to assess the overall response rate in NTRK fusion cancer
      patients as determined by an independent radiology committee (IRR). Secondary objectives of
      Phase 2 comprise the safety and efficacy of selitrectinib at the recommended dose.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Cancer patients <12 yearsExperimentalDose escalation cohorts with pediatric patients aged <12 years. Dose escalation starts with 43 mg of selitrectinib per m2 body surface twice daily.
  • Selitrectinib (BAY2731954)
Phase 1: Cancer patients ≥12 yearsExperimentalDose escalation cohorts with patients aged 12 years or older. Dose escalation starts with 100 mg of selitrectinib twice daily.
  • Selitrectinib (BAY2731954)
Phase 2: Cancer patients_Cohort 1ExperimentalExpansion cohort consisting of patients with NTRK fusion cancers showing disease progression despite treatment with a TRK inhibitor. Patients receive selitrectinib at recommended dose twice daily.
  • Selitrectinib (BAY2731954)
Phase 2: Cancer patients_Cohort 2ExperimentalExpansion cohort consisting of patients with NTRK fusion cancers showing intolerance or unresponsiveness to previous treatment with a TRK inhibitor. Patients receive selitrectinib at recommended dose twice daily.
  • Selitrectinib (BAY2731954)

Eligibility Criteria

        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 equivalent) laboratory.
             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 ≤ 3 (age ≥ 16
             years) or Lansky Performance Score (LPS) ≥ 40% (age < 16 years). If enrolled with
             primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) (age ≥ 16
             years) or LPS (age < 16 years) ≥ 50%.

          -  Life expectancy > 4 weeks.

          -  Adequate hematologic, hepatic and renal function.

          -  Patients with stable 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, TPX-0005).
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:1 Month
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Maximum tolerated dose (MTD)
Time Frame:Up to 42 days
Safety Issue:
Description:ORR is determined by an Independent Radiology Committee (IRR) using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Secondary Outcome Measures

Measure:Phase 1: Incidence of adverse events
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Phase 1: Severity of adverse events
Time Frame:Up to 56 months
Safety Issue:
Description:Severity is assessed using CTCAE version 4.03
Measure:Phase 1: Duration of adverse events
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Phase 1: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Phase 1: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 56 months
Safety Issue:
Description:
Measure:Phase 1: Overall response rate (ORR) in patients with NTRK fusion cancer previously treated with TRK inhibitor determined by investigator
Time Frame:Up to 56 months
Safety Issue:
Description:ORR is determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Phase 1: Overall response rate (ORR) in patients with primary central nervous system (CNS) malignancies determined by investigator
Time Frame:Up to 56 months
Safety Issue:
Description:ORR is determined by the treating investigator using the Response Assessment in Neuro-Oncology (RANO) criteria.
Measure:Phase 1: Overall survival (OS)
Time Frame:Up to 56 months
Safety Issue:
Description:Number of months from the initiation of selitrectinib to the date of death due to any cause.
Measure:Phase 1: Maximum concentration of BAY2731954 in plasma (Cmax)
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)
Safety Issue:
Description:
Measure:Phase 1: Area under the concentration versus time curve of BAY2731954 in plasma (AUC(0-last))
Time Frame:Predose, 0.25, 0.5, 1, 2, 4, 5, 8 and 10 hours post-dose on Days 1, 8, 15 and 22 of Cycle 1 (cycle length 28 days)
Safety Issue:
Description:
Measure:Phase 2: Incidence of adverse events in patients ≥12 years
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Severity of adverse events in patients ≥12 years
Time Frame:Up to 44 months
Safety Issue:
Description:Severity is assessed using CTCAE version 4.03
Measure:Phase 2: Duration of adverse events in patients ≥12 years
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Incidence of adverse events in patients <12 years
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Severity of adverse events in patients <12 years
Time Frame:Up to 44 months
Safety Issue:
Description:Severity is assessed using CTCAE version 4.03
Measure:Phase 2: Duration of adverse events in patients <12 years
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Overall response rate (ORR) in Cohort 2 determined by IRR
Time Frame:Up to 44 months
Safety Issue:
Description:ORR is determined by an Independent Radiology Committee (IRR) using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Measure:Phase 2: Overall response rate (ORR) determined by investigator
Time Frame:Up to 44 months
Safety Issue:
Description:ORR is determined by the treating investigator using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or the Response Assessment in Neuro-Oncology (RANO) criteria, as appropriate.
Measure:Phase 2: Duration of response (DOR) determined by IRR
Time Frame:Up to 44 months
Safety Issue:
Description:Determined by an Independent Radiology Committee (IRR)
Measure:Phase 2: Duration of response (DOR) determined by investigator
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Progression free survival (PFS) determined by IRR
Time Frame:Up to 44 months
Safety Issue:
Description:Determined by an Independent Radiology Committee (IRR)
Measure:Phase 2: Progression free survival (PFS) determined by investigator
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Overall survival (OS)
Time Frame:Up to 44 months
Safety Issue:
Description:
Measure:Phase 2: Clinical benefit rate (CBR) determined by IRR
Time Frame:Up to 44 months
Safety Issue:
Description:Determined by an Independent Radiology Committee (IRR)
Measure:Phase 2: Clinical benefit rate (CBR) determined by investigator
Time Frame:Up to 44 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bayer

Trial Keywords

  • Solid Tumor
  • Metastatic cancer
  • Advanced cancer
  • Neurotrophic tyrosine receptor kinase (NTRK)
  • NTRK1
  • NTRK2
  • NTRK3
  • Fusion Positive
  • Children

Last Updated

March 3, 2020