Trial Condition(s):

Solid tumors harboring NTRK fusion

A study to test the safety and efficacy of the drug larotrectinib for the treatment of tumors with NTRK-fusion in children (SCOUT)

Bayer Identifier:

20290

ClinicalTrials.gov Identifier:

NCT02637687

EudraCT Number:

2016-003498-16

Recruiting

Trial Purpose

The study is being done to test the safety of a cancer drug called larotrectinib in children. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.
The first study part (Phase 1) is done to determine what dose level of larotrectinib is safe for children, how the drug is absorbed and changed by their bodies and how well the cancer responds to the drug. The main purpose of the second study part (Phase 2) is to investigate how well and how long different cancer types respond to the treatment with larotrectininb.

Inclusion Criteria
- Phase 1 (Closed): 
                -- Dose escalation: Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists; OR Infants from birth and older with a diagnosis of malignancy and with a documented NTRK fusion that has progressed or was nonresponsive to available therapies, and for which no standard or available curative therapy exists; OR Patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection. Phase I dose escalation cohorts are closed to enrollment.
                -- Dose expansion: In addition to the above stated inclusion criteria, patients must have a malignancy with a documented NTRK gene fusion with the exception of patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer. Patients with infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer may enroll into this cohort with documentation of an ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing.
                - Phase 2:
                -- Infants from birth and older at C1D1 with a locally advanced or metastatic infantile fibrosarcoma, patients with locally advanced infantile fibrosarcoma who would require, in the opinion of the investigator, disfiguring surgery or limb amputation to achieve a complete surgical resection; OR Birth through 21 years of age at C1D1 with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion (or in the case of infantile fibrosarcoma, congenital mesoblastic nephroma or secretory breast cancer with documented ETV6 rearrangement (or NTRK3 rearrangement after discussion with the sponsor) by FISH or RT-PCR or a documented NTRK fusion by next generation sequencing) (identified through molecular assays as routinely performed at CLIA or other similarly certified laboratories). Patients with NTRK-fusion positive benign tumors are also eligible; OR Potential patients older than 21 years of age with a tumor diagnosis with histology typical of a pediatric patient and an NTRK fusion may be considered for enrollment following discussion between the local site Investigator and the Sponsor.
                - Patients with primary CNS tumors or cerebral metastasis
                - Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50.
                - Adequate hematologic function
                - Adequate hepatic and renal function
Exclusion Criteria
- Major surgery within 14 days (2 weeks) prior to C1D1
                - Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1, ongoing cardiomyopathy; current prolonged QTc interval > 480 milliseconds
                - Active uncontrolled systemic bacterial, viral, or fungal infection
                - Current treatment with a strong CYP3A4 inhibitor or inducer. Enzyme-inducing anti-epileptic drugs (EIAEDs) and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed.
                - Phase 2 only: 
                -- Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting TRK, including entrectinib, crizotinib and lestaurtinib. Patients who received a TRK inhibitor for less than 28 days of treatment and discontinued because of intolerance remain eligible.

Trial Summary

Enrollment Goal
155
Trial Dates
black-arrow
Phase
1/2
Could I receive a placebo?
No
Products
Vitrakvi (Larotrectinib, BAY2757556)
Accepts Healthy Volunteers
No

Where to Participate

Loading...
Locations
Status
LocationsStatus
Locations

Institut Curie - Ulm - Paris

PARIS cedex 5, France, 75248

Status
Recruiting
 
Locations

Institut Gustave Roussy

VILLEJUIF CEDEX, France, 94805

Status
Recruiting
 
Locations

Uniwersyteckie Centrum Kliniczne

Gdansk, Poland, 80-952

Status
Recruiting
 
Locations

Karolinska Universitetssjukhuset i Solna

Stockholm, Sweden, 171 76

Status
Recruiting
 
Locations

Clalit Health Services Schneider Children's Medical Center

Petach Tikva, Israel, 4920235

Status
Active, not recruiting
 
Locations

Sydney Children’s Hospital

Sydney, Australia, 2031

Status
Recruiting
 
Locations

Royal Children's Hospital Melbourne

Parkville, Australia, 3052

Status
Recruiting
 
Locations

Universitätskinderspital Zürich

Zürich, Switzerland, 8032

Status
Recruiting
 
Locations

Rigshospitalet, Dept Pediatrics & Adelescent Med.

Copenhagen, Denmark, 2100

Status
Recruiting
 
Locations

Nemours Children’s Hospital (Orlando)

Orlando, United States, 32827

Status
Completed
 
Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milano, Italy, 20133

Status
Recruiting
 
Locations

A.O.U. di Padova

Padova, Italy, 35128

Status
Not yet recruiting
 
Locations

Royal Marsden NHS Trust (Surrey)

Sutton, United Kingdom, SM2 5PT

Status
Recruiting
 
Locations

Our Lady's Hospital For Sick Children

Crumlin, Ireland, 12

Status
Recruiting
 
Locations

University of Texas Southwestern Medical Center

Dallas, United States, 75235

Status
Active, not recruiting
 
Locations

Children's Hospital of Los Angeles

Los Angeles, United States, 90027

Status
Active, not recruiting
 
Locations

Boston hildren's Hospital

Boston, United States, 02115

Status
Active, not recruiting
 
Locations

Memorial Sloan Kettering Cancer Center

New York, United States, 10065

Status
Active, not recruiting
 
Locations

St. Jude Children's Research Hospital

Memphis, United States, 38105

Status
Active, not recruiting
 
Locations

Seattle Children's Hospital

Seattle, United States, 98105

Status
Active, not recruiting
 
Locations

Cincinnati Children's Hospital and Medical Center

Cincinnati, United States, 45229-3039

Status
Completed
 
Locations

UCLA Jonsson Comprehensive Cancer Center

Los Angeles, United States, 90095

Status
Active, not recruiting
 
Locations

Lucille Salter Packard Children's Hospital at Stanford

Palo Alto, United States, 94304

Status
Active, not recruiting
 
Locations

Tianjin Medical University Cancer Institiute & Hospital

Tianjin, China, 300060

Status
Recruiting
 
Locations

Beijing Children's Hospital, Capital Medical University

Beijing, China, 100045

Status
Recruiting
 
Locations

National Cancer Center Hospital

Chuo-ku, Japan, 104-0045

Status
Active, not recruiting
 
Locations

Sun Yat-sen University Cancer Center

Guangzhou, China, 510060

Status
Recruiting
 
Locations

The Hospital for Sick Children (SickKids)

Toronto, Canada, M5G 1X8

Status
Recruiting
 
Locations

CHU Sainte-Justine

Montreal, Canada, H3T 1C5

Status
Recruiting
 
Locations

Charité - Campus Virchow-Klinikum (CVK)

Berlin, Germany, 13353

Status
Recruiting
 
Locations

Olgahospital

Stuttgart, Germany, 70174

Status
Recruiting
 
Locations

Universitätsklinikum Heidelberg

Heidelberg, Germany, 69120

Status
Recruiting
 
Locations

Ciutat Sanitària i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08035

Status
Recruiting
 
Locations

Prinses Maxima Centrum

UTRECHT, Netherlands, 3584 CS

Status
Recruiting
 
Locations

Seoul National University Hospital

Seoul, South Korea, 03080

Status
Recruiting
 
Locations

Severance Hospital, Yonsei University Health System

Seoul, South Korea, 03722

Status
Not yet recruiting
 
Locations

Kanagawa Children's Medical Center

Yokohama, Japan, 232-8555

Status
Active, not recruiting
 
Locations

Kyushu University Hospital

Fukuoka, Japan, 812-8582

Status
Completed
 
Locations

British Columbia Childrens Hospital

Vancouver, Canada, V6H 3V4

Status
Not yet recruiting
 
Locations

Children's Hospital of Philadelphia

Philadelphia, United States, 19104

Status
Not yet recruiting
 
Locations

Fakultni nemocnice v Motole

Praha 5, Czech Republic, 150 06

Status
Recruiting
 
Locations

FN Brno - Detska nemocnice

Brno, Czech Republic, 625 00

Status
Not yet recruiting
 
Locations

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, Turkey, 34093

Status
Recruiting
 
Locations

Center of Pediatric Hematology, Oncology and Immunology

Moscow, Russia, 117997

Status
Not yet recruiting
 
Locations

WESTERN UKRAINIAN SPECIALIZED PEDIATRIC MEDICAL CENTRE

Lviv, Ukraine, 79035

Status
Recruiting
 
Locations

National Cancer Institute-Ukraine

Kiev, Ukraine, 03022

Status
Not yet recruiting
 
Locations

Morozov Children's City Clinical Hospital

Moscow, Russia, 119049

Status
Not yet recruiting
 
Locations

Women's and Children's Hospital

North Adelaide, Australia, 5006

Status
Not yet recruiting
 

Trial Design