Clinical Trial - NCT03215511

       

A Study to Test the Safety of the Investigational Drug Selitrectinib 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: Bayer
Disease Program: Phase I

Next Steps


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




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.
Condition Title Intervention Phase
Solid Tumors Harboring NTRK Fusion Selitrectinib (BAY2731954) Phase 1/Phase 2
Study Type Interventional
Official Title A Phase 1/2 Study of the TRK Inhibitor Selitrectinib 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 IRR [Time Frame: Up to 40 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) for patient =12 years from Cohort 1 by IRR [Time Frame: Up to 40 months] [Designated as safety issue: ]


Secondary Outcome Measures

Phase 1: Incidence of adverse events [Time Frame: Up to 56 months] [Designated as safety issue: ]

Phase 1: Severity of adverse events [Time Frame: Up to 56 months] [Designated as safety issue: ]

Phase 1: Duration of adverse events [Time Frame: Up to 56 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 56 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 56 months] [Designated as safety issue: ]

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] [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 56 months] [Designated as safety issue: ]

Phase 1: Overall survival (OS) [Time Frame: Up to 56 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: 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)] [Designated as safety issue: ]

Phase 2: Incidence of adverse events in patients =12 years [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Severity of adverse events in patients =12 years [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Duration of adverse events in patients =12 years [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Incidence of adverse events in patients <12 years [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Severity of adverse events in patients <12 years [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Duration of adverse events in patients <12 years [Time Frame: Up to 44 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 44 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 44 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) in Cohort 2 determined by IRR [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Overall response rate (ORR) determined by investigator [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Duration of response (DOR) determined by IRR [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Duration of response (DOR) determined by investigator [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Progression free survival (PFS) determined by IRR [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Progression free survival (PFS) determined by investigator [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Overall survival (OS) [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Clinical benefit rate (CBR) determined by IRR [Time Frame: Up to 44 months] [Designated as safety issue: ]

Phase 2: Clinical benefit rate (CBR) determined by investigator [Time Frame: Up to 44 months] [Designated as safety issue: ]

Estimated Enrollment: 170
Study Start Date: July 2017
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: October 2021
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 selitrectinib per m2 body surface twice daily.
Drug:Selitrectinib (BAY2731954)
Selitrectinib 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 selitrectinib 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 selitrectinib 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 selitrectinib 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 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 Score (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.

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
    • UCSF Med Center Helen Diller Family Comp Cancer Center San Francisco, California, United States, 94158
  • United States, Colorado
    • Sarah Cannon Research Institute at HealthONE Denver, Colorado, United States, 80218
  • United States, Georgia
    • Children's Healthcare of Atlanta Atlanta, Georgia, United States, 30329
  • 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, North Carolina
    • Levine Cancer Institute Charlotte, North Carolina, United States, 28204-2990
    • Duke University Medical Center Durham, North Carolina, United States, 27710
  • United States, Ohio
    • University Hospitals Cleveland Medical Center Cleveland, Ohio, United States, 44106-2602
  • United States, Oregon
    • Oregon Health and Science University Portland, Oregon, United States, 97239
  • United States, Pennsylvania
    • Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104
    • Eastern Regional Medical Center Philadelphia, Pennsylvania, United States, 19124
  • United States, South Dakota
    • Avera Cancer Institute Sioux Falls, South Dakota, United States, 57105
  • 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
  • United States, Wisconsin
    • University of Wisconsin - Madison Madison, Wisconsin, United States, 53792
  • Australia, New South Wales
    • Sydney Children's Hospital Sydney, New South Wales, Australia, 2031
  • Australia, Victoria
    • Austin Health Heidelberg, Victoria, Australia, 3084
    • Royal Children's Hospital Melbourne Parkville, Victoria, Australia, 3052
  • Belgium,
    • UZ Antwerpen Edegem, , Belgium, 2650
  • Canada, Ontario
    • Sunnybrook Health Sciences Centre Toronto, Ontario, Canada, M4N 3M5
  • Canada, Quebec
    • CHU Sainte-Justine Montreal, Quebec, Canada, H3T 1C5
    • McGill University Health Center Montreal, Quebec, Canada, H4A 3J1
  • China, Sichuan
    • West China Hospital, Sichuan University Chengdu, Sichuan, China, 610041
  • China, Zhejiang
    • Zhejiang Cancer Hospital Hangzhou, Zhejiang, China, 310022
  • China,
    • Beijing Cancer Hospital Beijing, , China, 100142
    • Zhongshan Hospital, Fudan University Shanghai, , China, 200032
  • Denmark,
    • Finsen Centre Copenhagen, , Denmark, 2100
  • France,
    • Institut Bergonié - Unicancer Nouvelle Aquitaine Bordeaux Cedex, , France, 33076
    • Institut Curie - Ulm - Paris Paris, , France, 75005
    • Institut Gustave Roussy Villejuif, , France, 94805
  • Germany, Baden-Württemberg
    • Universitätsklinikum Heidelberg Heidelberg, Baden-Württemberg, Germany, 69120
  • Germany,
    • Charité Comprehensive Cancer Center (CCCC) Berlin, , Germany, 12203
  • Hong Kong,
    • Queen Mary Hospital Hong Kong, , Hong Kong,
    • Prince of Wales Hospital Shatin, , Hong Kong,
  • Ireland,
    • Tallaght Hospital Dublin, , Ireland, 24
  • 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
    • KK Women's and Children's Hospital Singapore, , Singapore, 229899
  • 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 February 25, 2021