Clinical Trial - NCT03215511

A Study to Test the Safety of the Investigational Drug Loxo-195 in Children and Adults That May Treat Cancer

Recruiting

Sponsor: Bayer

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT03215511

Protocol Info

Short Description: Phase 1/2 of LOXO-195 in NTRK Fusion or Non-Fusion NTRK Altered Cancers
Long Description: A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects with Previously Treated NTRK Fusion Cancers
MGH Status: Open
Sponsor: Loxo Oncology Inc.
Disease Program: Phase I

Next Steps


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Purpose

This research study is done to test the safety of the new drug Loxo-195 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 Loxo-195 in humans with cancer, for whom no other effective therapy exists.
Condition Title Intervention Phase
Solid Tumors Harboring NTRK Fusion BAY2731954 Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1/2 Study of the TRK Inhibitor LOXO-195 in Adult and Pediatric Subjects With Previously Treated NTRK Fusion Cancers

Primary Outcome Measures

Phase 1: Maximum tolerated dose (MTD) [Time Frame: Up to 42 days] [Designated as safety issue: ]

Phase 1: Recommended dose [Time Frame: Up to 12 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) for patients <12 years from Cohort 1 by IRC [Time Frame: Up to 14 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) for patient ≥12 years from Cohort 1 by IRC [Time Frame: Up to 14 months] [Designated as safety issue: ]


Secondary Outcome Measures

Phase 1: Incidence of adverse events [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Severity of adverse events [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Duration of adverse events [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Overall response rate (ORR) in patients with NTRK fusion cancer previously treated with TRK inhibitor determined by an IRC [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Overall response rate (ORR) in patients with primary central nervous system (CNS) malignancies determined by investigator [Time Frame: Up to 30 months] [Designated as safety issue: ]

Phase 1: Overall survival (OS) [Time Frame: Up to 30 months] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

Phase 1: Time to maximum concentration of BAY2731954 in plasma (Tmax) [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)] [Designated as safety issue: ]

Phase 1: Area under the concentration versus time curve of BAY2731954 in plasma (AUC(0-t)) [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)] [Designated as safety issue: ]

Phase 1: Area under the concentration versus time curve of BAY2731954 in plasma from time 0 to infinity (AUC(0-∞)) [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)] [Designated as safety issue: ]

Phase 1: Apparent volume of distribution (Vz/F) [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)] [Designated as safety issue: ]

Phase 1: Clearance (CL/F) [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)] [Designated as safety issue: ]

Phase 1: Terminal elimination half-life (T1/2) [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)] [Designated as safety issue: ]

Phase 2: Incidence of adverse events in patients ≥12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Severity of adverse events in patients ≥12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Duration of adverse events in patients ≥12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Incidence of adverse events in patients <12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Severity of adverse events in patients <12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Duration of adverse events in patients <12 years [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) in Cohort 2 determined by IRC [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) in Cohort 1 determined by investigator [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) in Cohort 2 determined by investigator [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Duration of response (DOR) determined by IRC [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Duration of response (DOR) determined by investigator [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Progression free survival (PFS) determined by IRC [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Progression free survival (PFS) determined by investigator [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Overall survival (OS) [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Clinical benefit rate (CBR) determined by IRC [Time Frame: Up to 18 months] [Designated as safety issue: ]

Phase 2: Clinical benefit rate (CBR) determined by investigator [Time Frame: Up to 18 months] [Designated as safety issue: ]

Estimated Enrollment: 93
Study Start Date: July 2017
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: August 2019
Arms Assigned Interventions

Experimental:Phase 1: Cancer patients <12 years

Dose escalation cohorts with pediatric patients aged <12 years. Dose escalation starts with 43 mg of BAY2731954 per m2 body surface twice daily (children <3 years: once daily).
Drug:BAY2731954
BAY2731954 is administered as capsules or liquid formulation.

Experimental:Phase 1: Cancer patients ≥12 years

Dose escalation cohorts with patients aged 12 years or older. Dose escalation starts with 100 mg of BAY2731954 twice daily.

Experimental:Phase 2: Cancer patients_Cohort 1

Expansion cohort consisting of patients with NTRK fusion cancers showing disease progression despite treatment with a TRK inhibitor. Patients receive BAY2731954 at recommended dose twice daily.

Experimental:Phase 2: Cancer patients_Cohort 2

Expansion cohort consisting of patients with NTRK fusion cancers showing intolerance or unresponsiveness to previous treatment with a TRK inhibitor. Patients receive BAY2731954 at recommended dose twice daily.

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly 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 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 LOXO-195
  • Ability to receive study drug orally or by enteral administration

Exclusion Criteria:

  • Concurrent treatment with a strong CYP3A4 inhibitor or inducer or drugs associated with QT prolongation.
  • Clinically significant active cardiovascular disease or history of myocardial infarction within 3 months prior to planned start of LOXO-195, 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 LOXO-195 or Ora-Sweet® SF and OraPlus® for patients receiving liquid formulation.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT03215511

Locations

  • United States, California
    • Univ.of California-San Diego Moores Cancer Center La Jolla, California, United States, 92093
    • UCLA Jonsson Comprehensive Cancer Center Los Angeles, California, United States, 90095
    • Stanford Cancer Center Palo Alto, California, United States, 94304
  • United States, Colorado
    • Sarah Cannon Research Institute at HealthONE Denver, Colorado, United States, 80218
  • United States, Illinois
    • Midwestern Regional Medical Center Zion, Illinois, United States, 60099
  • United States, Louisiana
    • Ochsner Medical Center - New Orleans New Orleans, Louisiana, United States, 70121
  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114-2696
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
  • United States, New York
    • Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10065
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97201
  • United States, Pennsylvania
    • Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104
    • Eastern Regional Medical Center Philadelphia, Pennsylvania, United States, 19124
  • United States, Tennessee
    • St. Jude Children's Research Hospital Memphis, Tennessee, United States, 38105
    • Sarah Cannon Research Institute Nashville, Tennessee, United States, 37203
  • United States, Texas
    • University of Texas Southwestern Medical Center Dallas, Texas, United States, 75235
    • University of Texas Southwestern Medical Center Dallas, Texas, United States, 75390
    • University of Texas MD Anderson Cancer Center Houston, Texas, United States, 77030-4000
  • United States, Utah
    • University of Utah Salt Lake City, Utah, United States, 84112
  • United States, Virginia
    • Virginia Oncology Associates Norfolk, Virginia, United States, 23502
  • United States, Washington
    • Seattle Children's Hospital Seattle, Washington, United States, 98105
  • Australia, New South Wales
    • Westmead Hospital Randwick, New South Wales, Australia, 2031
  • Australia, Victoria
    • Austin Health Heidelberg, Victoria, Australia, 3084
  • Denmark,
    • Finsen Centre Copenhagen, , Denmark, 2100
  • France,
    • Institut Curie - Ulm - Paris Paris, , France, 75005
    • Institut Gustave Roussy Villejuif, , France, 94805
  • Germany, Baden-Württemberg
    • Universitätsklinikum Heidelberg Heidelberg, Baden-Württemberg, Germany, 69120
  • Italy, Lombardia
    • Fondazione IRCCS Istituto Nazionale dei Tumori Milano, Lombardia, Italy, 20133
  • Korea, Republic of,
    • Seoul National University Hospital Seoul, , Korea, Republic of, 03080
  • Singapore,
    • National Cancer Center Singapore, , Singapore, 169610
  • Spain,
    • Ciutat Sanitària i Universitaria de la Vall d'Hebron Barcelona, , Spain, 08035
    • Ciutat Sanitària i Universitaria de la Vall d'Hebron Barcelona, , Spain, 08035
    • Fundacion Jimenez Diaz (Clinica de la Concepcion) Madrid, , Spain, 28040
  • United Kingdom,
    • Sarah Cannon Research Institute UK Ltd London, , United Kingdom, W1G 6AD

Sponsors and Collaborators

Bayer

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT03215511
Other Study ID Numbers: LOXO-EXT-17005
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Bayer:

Solid Tumor

Metastatic cancer

Advanced cancer

Neurotrophic tyrosine receptor kinase (NTRK)

NTRK1

NTRK2

NTRK3

Fusion Positive

Children

Additional relevant MeSH terms:

9-Fluoro-15-methyl-2,11,16,20,21,24-hexaazapentacyclo(16.5.2.02,6.07,12.021,25)pentacosa-1(24),7,9,11,18(25),19,22-heptaen-17-one

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on July 18, 2019