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

NCT03215511 | Completed Phase 1 FDA Drug

• 3 other identifiers: 20810LOXO-EXT-170052017-004246-20
• Study Type: interventional
• Target: 81
• Locations: 10 countries
• Sites: 29

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.

Conditions

Solid Tumors Harboring NTRK Fusion

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  Up to 42 days

• Recommended dose

  Up to 12 months

Secondary Outcomes (9)

• Incidence of adverse events

  Up to 56 months

• Severity of adverse events

  Up to 56 months

• Duration of adverse events

  Up to 56 months

• Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration

  Up to 56 months

• Severity of safety-relevant changes in clinical parameters or vital signs after drug administration

  Up to 56 months

Study Arms (2)

Cancer participants <12 years

EXPERIMENTAL

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)

Cancer participants ≥12 years

EXPERIMENTAL

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)

Interventions

Selitrectinib (BAY2731954) DRUG

Selitrectinib is administered as capsules or liquid formulation.

Also known as: Loxo-195

Cancer participants <12 years; Cancer participants ≥12 years

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead

Study Sites (29)

Univ.of California-San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095-1781, United States

Location

Stanford Cancer Center

Palo Alto, California, 94304, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114-2696, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Sydney Children's Hospital

Sydney, New South Wales, 2031, Australia

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Rigshospitalet - Kræftbehandling

Copenhagen, 2100, Denmark

Location

Institut Curie - Ulm - Paris

Paris, 75248, France

Location

Institut Gustave Roussy - Département de Médecine Oncologique

Villejuif, 94805, France

Location

Universitätsklinikum Heidelberg

Heidelberg, Baden-Wurttemberg, 69115, Germany

Location

Tallaght Hospital

Dublin, D24NR0A, Ireland

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Lombardy, 20133, Italy

Location

National Cancer Center Singapore

Singapore, 168583, Singapore

Location

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, 28040, Spain

Location

Related Publications (1)

• O'Reilly EM, Hechtman JF. Tumour response to TRK inhibition in a patient with pancreatic adenocarcinoma harbouring an NTRK gene fusion. Ann Oncol. 2019 Nov 1;30(Suppl_8):viii36-viii40. doi: 10.1093/annonc/mdz385. Epub 2019 Dec 24.

  PMID: 31605106 DERIVED

Related Links

• Click here to find further information and, after study completion, the study results according to Bayer's transparency standards
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

selitrectinib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 12, 2017
• Study Start: July 3, 2017
• Primary Completion: April 11, 2022
• Study Completion: January 30, 2023
• Last Updated: October 30, 2024

Record last verified: 2024-10

Locations

DE (1); IT (1); US (17); DK (1); ES (2); IE (1); AU (2); FR (2); SG (1); BE (1)