A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

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A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children

Study 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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	N/A - 21 Years
Gender	All

More Inclusion & Exclusion Criteria

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.

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 Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT02637687
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Bayer
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Active, not recruiting
Countries	Australia, Canada, China, Czechia, Denmark, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, Poland, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), Ukraine, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Solid Tumors Harboring NTRK Fusion

Arms & Interventions

Arms

Experimental: Phase 1 dose escalation

Patients will receive the different levels of dose on Day 1 (BID in accordance with the cohort assignment). Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed)

Experimental: Phase 1 dose expansion

Patients who are enrolled in the expansion cohort, following the formal dose escalation phase of the study. Distinct from the Phase 1 dose escalation cohort, the Phase 1 expansion cohort will enroll pediatric patients with advanced solid or primary CNS tumors with a documented NTRK gene fusion, or in the case of IFS, CMN or SBC with documented ETV6 rearrangement by FISH or RT-PCR or a documented NTRK fusion by NGS. This expansion cohort will follow the same schedule of assessments as the dose escalation cohorts. (arm closed)

Experimental: Phase 2: Patients with tumors bearing NTRK fusions (IFS)_Cohort 1

Patients will receive larotrectinib dose on Day 1 (BID in accordance with the cohort assignment) at the recommended Phase 2 dose as determined in the Phase 1 portion of this study. Each cycle will consist of 28 days of continuous dosing. Individual patients will continue daily larotrectinib dosing until PD, unacceptable toxicity, or other reason for treatment discontinuation. (arm closed)

Experimental: Phase 2: Other extra-cranial solid tumors_Cohort 2

Experimental: Phase 2: Primary CNS tumors_Cohort 3

Experimental: Phase 2: Bone health assessment_sub-cohort

Interventions

Drug: - Larotrectinib (Vitrakvi, BAY2757556)

BAY2757556 will be administered orally as capsule or in liquid form over continuous 28-day cycles.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles 5368361, California 5332921

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Address

Children's Hospital Los Angeles - Hematology/Oncology

Los Angeles 5368361, California 5332921, 90027

UCLA Jonsson Comprehensive Cancer Center, Los Angeles 5368361, California 5332921

Status

Address

UCLA Jonsson Comprehensive Cancer Center

Los Angeles 5368361, California 5332921, 90095-1781

Palo Alto 5380748, California 5332921

Status

Address

Lucille Packard Children's Hospital Stanford - Pediatric Nephrology

Palo Alto 5380748, California 5332921, 94304

Orlando 4167147, Florida 4155751

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Address

Nemours Children's Hospital - Florida - Hematology / Oncology

Orlando 4167147, Florida 4155751, 32827

Dana-Farber Cancer Institute, Boston 4930956, Massachusetts 6254926

Status

Address

Dana-Farber Cancer Institute

Boston 4930956, Massachusetts 6254926, 02215

New York 5128581, New York 5128638

Status

Address

Memorial Sloan Kettering Cancer Center New York - Main Campus

New York 5128581, New York 5128638, 10065

Cincinnati 4508722, Ohio 5165418

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Address

Cincinnati Children's Hospital Medical Center | Division of Nephrology and Hypertension

Cincinnati 4508722, Ohio 5165418, 45229

Philadelphia 4560349, Pennsylvania 6254927

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Address

Children's Hospital of Philadelphia - Hematology/Oncology

Philadelphia 4560349, Pennsylvania 6254927, 19104

St. Jude Children's Research Hospital, Memphis 4641239, Tennessee 4662168

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Address

St. Jude Children's Research Hospital

Memphis 4641239, Tennessee 4662168, 38105

Dallas 4684888, Texas 4736286

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Address

University of Texas Southwestern Medical Center

Dallas 4684888, Texas 4736286, 75390

Seattle Children's Hosptial - Oncology, Seattle 5809844, Washington 5815135

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Address

Seattle Children's Hosptial - Oncology

Seattle 5809844, Washington 5815135, 98105

International Sites

Sydney Children's Hospital, Sydney 2147714, New South Wales 2155400, Australia

Status

Address

Sydney Children's Hospital

Sydney 2147714, New South Wales 2155400, 2031

Women's and Children's Hospital, North Adelaide 8469169, South Australia 2061327, Australia

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Address

Women's and Children's Hospital

North Adelaide 8469169, South Australia 2061327, 5006

Royal Children's Hospital Melbourne, Parkville 2153770, Victoria 2145234, Australia

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Address

Royal Children's Hospital Melbourne

Parkville 2153770, Victoria 2145234, 3052

Vancouver 6173331, British Columbia 5909050, Canada

Status

Address

BC Children's Hospital - Hematology/Oncology

Vancouver 6173331, British Columbia 5909050, V6H 3N1

Toronto 6167865, Ontario 6093943, Canada

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Address

The Hospital for Sick Children (SickKids)

Toronto 6167865, Ontario 6093943, M5G 1X8

CHU Sainte-Justine, Montreal 6077243, Quebec 6115047, Canada

Status

Address

CHU Sainte-Justine

Montreal 6077243, Quebec 6115047, H3T 1C5

Beijing 1816670, Beijing Municipality 2038349, China

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Address

Beijing Children's Hospital, Capital Medical University

Beijing 1816670, Beijing Municipality 2038349, 100045

Sun Yat-sen University Cancer Center, Guangzhou 1809858, Guangdong 1809935, China

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Address

Sun Yat-sen University Cancer Center

Guangzhou 1809858, Guangdong 1809935, 510000

Tianjin 1792947, China

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Address

Tianjin Medical University Cancer Institute & Hospital

Tianjin 1792947, , 300000

FN Brno - Detska nemocnice, Brno 3078610, Czechia

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Address

FN Brno - Detska nemocnice

Brno 3078610, , 613 00

Fakultni nemocnice v Motole, Prague 3067696, Czechia

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Address

Fakultni nemocnice v Motole

Prague 3067696, , 150 06

Rigshospitalet - Børn og Unge, Copenhagen 2618425, Denmark

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Address

Rigshospitalet - Børn og Unge

Copenhagen 2618425, , 2100

Institut Curie - Ulm - Paris, Paris 2988507, France

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Address

Institut Curie - Ulm - Paris

Paris 2988507, , 75248

Villejuif 2968705, France

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Address

Gustave Roussy - Departement Oncologie-Radiotherapie

Villejuif 2968705, , 94805

Heidelberg 2907911, Baden-Wurttemberg 2953481, Germany

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Address

Universitaetsklinikum Heidelberg - KiTZ | Klinik für Paediatrische Onkologie, Haematologie, Immunologie und Pneumologie

Heidelberg 2907911, Baden-Wurttemberg 2953481, 69120

Stuttgart 2825297, Baden-Wurttemberg 2953481, Germany

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Address

KLINIKUM STUTTGART - Olgahospital | Paediatrie 5 (Onkologie, Haematologie, Immunologie)

Stuttgart 2825297, Baden-Wurttemberg 2953481, 70174

Berlin 2950159, Germany

Status

Address

Charité - Campus Virchow-Klinikum (CVK), Klinik für Pädiatrie mit Schwerpunkt Onkologie und Hämatologie

Berlin 2950159, , 13353

Children's Health Ireland Crumlin, Crumlin 2964963, Dublin, Ireland

Status

Address

Children's Health Ireland Crumlin

Crumlin 2964963, Dublin, 12

Petah Tikva 293918, Israel

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Address

Clalit Health Services Schneider Children's Medical Center

Petah Tikva 293918, , 4920235

Milan 3173435, Lombardy 3174618, Italy

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Address

Fondazione IRCCS Istituto Nazionale dei Tumori - S. C. Pediatria Oncologica

Milan 3173435, Lombardy 3174618, 20133

Kanagawa Children's Medical Center, Yokohama 1848354, Kanagawa 1860291, Japan

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Address

Kanagawa Children's Medical Center

Yokohama 1848354, Kanagawa 1860291, 252-8555

National Cancer Center Hospital, Chuo-ku, Tokyo 1850144, Japan

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Address

National Cancer Center Hospital

Chuo-ku, Tokyo 1850144, 104-0045

Kyushu University Hospital, Fukuoka 1863967, Japan

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Address

Kyushu University Hospital

Fukuoka 1863967, , 812-8582

Prinses Maxima Centrum, Utrecht 2745912, Netherlands

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Address

Prinses Maxima Centrum

Utrecht 2745912, , 3584 CS

Uniwersyteckie Centrum Kliniczne, Gdansk 3099434, Poland

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Address

Uniwersyteckie Centrum Kliniczne

Gdansk 3099434, , 80-214

Seoul 1835848, Seoul Teugbyeolsi, South Korea

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Address

Severance Hospital, Yonsei University Health System

Seoul 1835848, Seoul Teugbyeolsi, 03722

Seoul National University Hospital, Seoul 1835848, Seoul Teugbyeolsi, South Korea

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Address

Seoul National University Hospital

Seoul 1835848, Seoul Teugbyeolsi, 3080

Barcelona 3128760, Spain

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Address

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona 3128760, , 08035

Karolinska Universitetssjukhuset i Solna, Stockholm 2673730, Sweden

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Karolinska Universitetssjukhuset i Solna

Stockholm 2673730, , 171 76

Universitätskinderspital Zürich, Zurich 2657896, Switzerland

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Universitätskinderspital Zürich

Zurich 2657896, , 8032

Istanbul 745044, Turkey (Türkiye)

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Address

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul 745044, , 34093

Kyiv 703448, Ukraine

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Address

Governmental Noncommercial Institution "National Cancer Institute

Kyiv 703448, , 03022

Lviv 702550, Ukraine

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Address

Western Ukrainian Specialized Pediatric Medial Centre, Surgical Department

Lviv 702550, , 79035

Royal Marsden NHS Trust (Surrey), Sutton 2636503, Surrey, United Kingdom

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Address

Royal Marsden NHS Trust (Surrey)

Sutton 2636503, Surrey, SM2 5PT

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