Trial Condition(s):

Solid tumors harboring NTRK fusion

A study to test the effect of the drug larotrectinib in adults and children with NTRK-fusion positive solid tumors (NAVIGATE)

Bayer Identifier:

20289

ClinicalTrials.gov Identifier:

NCT02576431

EudraCT Number:

2015-003582-28

Recruiting

Trial Purpose

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Inclusion Criteria
- Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories.
 - Subjects who have received prior standard therapy appropriate for their tumor type and stage of disease, or who have no satisfactory alternative treatments and in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.
 - Subjects must have at least one measurable lesion as defined by RECIST v1.1. Subjects with solid tumors without RECIST v1.1 measurable disease (e.g., evaluable disease only) had been eligible for enrollment to Cohort 8 as per protocol versions 1.0 - 8.0, regardless of tumor type. Subjects with primary CNS tumors should meet the following criteria
a. Have received prior treatment including radiation and/or chemotherapy, with radiation completed > 12 weeks prior to C1D1 of therapy, as recommended or appropriate for that CNS tumor type.
b. Have ≥ 1 site of bi-dimensionally measurable disease (confirmed by magnetic resonance imaging [MRI] and evaluable by RANO criteria), with the size of at least one of the measurable lesions ≥ 1 cm in each dimension and noted on more than one imaging slice.
c. Imaging study performed within 28 days before enrollment. If on steroid therapy, the dose must be stable for at least 7 days immediately before and during the imaging study.
d. Must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.
For subjects eligible for enrollment to bone health cohort, inclusion criterion 3 is modified as the following:
 e. Subjects must have at least one lesion at baseline (measurable or non-measurable as defined by RECIST v1.1 or RANO criteria, as appropriate to tumor type).
 f. Subjects with primary CNS tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment.
- Performance Status: Eastern Cooperative Oncology Group (ECOG) score ≤ 3 If enrolled with primary CNS tumor to be assessed by RANO, Karnofsky Performance Score (KPS) ≥50% 
 - Tumor tissue before treatment (mandatory). If neither fresh tissue can be obtained nor archival tissue is available patients might be enrolled after consultation with the sponsor.
 - Willingness of men and women of reproductive potential to use double effective birth control methods, defined as one used by the subject and another by his/her partner, for the duration of treatment and for 1 month following study completion.
 - For subjects eligible for enrollment to bone health cohort only: life expectancy of at least 6 months, based on investigator assessment.
Exclusion Criteria
- Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (TRK). Subjects who received less than 28 days of treatment and discontinued because of intolerance or toxicity are eligible.
 - Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain metastases are eligible to participate in the study.) Subjects with primary central nervous system (CNS) tumors are eligible.
 - Pregnancy or lactation.
 - Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures.
 - Unstable cardiovascular disease is defined as:
 -- In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy.
 -- Myocardial infarction within 3 months of screening.
 -- Stroke within 3 months of screening.

Trial Summary

Enrollment Goal
204
Trial Dates
black-arrow
Phase
2
Could I receive a placebo?
No
Products
Vitrakvi (Larotrectinib, BAY2757556)
Accepts Healthy Volunteers
No

Where to Participate

Loading...
Locations
Status
LocationsStatus
Locations

Institut Bergonié - Unicancer Nouvelle Aquitaine

BORDEAUX CEDEX, France, 33076

Status
Recruiting
 
Locations

Finsen Centre

Copenhagen, Denmark, 2100

Status
Recruiting
 
Locations

National Cancer Center Hospital East

Kashiwa, Japan, 277-8577

Status
Active, not recruiting
 
Locations

UCLA-Santa Monica Medical Center

Santa Monica, United States, 90404

Status
Active, not recruiting
 
Locations

University of Texas MD Anderson Cancer Center

Houston, United States, 77030

Status
Recruiting
 
Locations

Massachusetts General Hospital

Boston, United States, 02114

Status
Active, not recruiting
 
Locations

Vanderbilt University Medical Center

Nashville, United States, 37232

Status
Active, not recruiting
 
Locations

Memorial Sloan-Kettering Cancer Center

New York, United States, 10065

Status
Active, not recruiting
 
Locations

Inova Schar Cancer Institute

Fairfax, United States, 22031

Status
Active, not recruiting
 
Locations

Fox Chase Cancer Center

Philadelphia, United States, 19111

Status
Completed
 
Locations

Thomas Jefferson University

Philadelphia, United States, 19107

Status
Active, not recruiting
 
Locations

Cleveland Clinic Foundation

Cleveland, United States, 44195-0002

Status
Completed
 
Locations

University of North Carolina Hospitals

Chapel Hill, United States, 27599

Status
Active, not recruiting
 
Locations

West Virginia University

Morgantown, United States, 26505

Status
Completed
 
Locations

Wake Forest Baptist Health

Winston-Salem, United States, 27157-1082

Status
Completed
 
Locations

Memorial Hospital West

Pembroke, United States, 33028

Status
Completed
 
Locations

Avera Cancer Institute

Sioux Falls, United States, 57105

Status
Completed
 
Locations

Dana-Farber Cancer Institute

Boston, United States, 02215

Status
Active, not recruiting
 
Locations

University of Washington

Seattle, United States, 98109

Status
Completed
 
Locations

Institute Of Cancer-Barts and The London School of Medicine

London, United Kingdom, EC1M 6BQ

Status
Recruiting
 
Locations

University College Hospital

London, United Kingdom, W1T 7HA

Status
Recruiting
 
Locations

University of Chicago

Chicago, United States, 60637

Status
Completed
 
Locations

St Vincents University Hospital

Dublin, Ireland, DUBLIN 4

Status
Recruiting
 
Locations

Stanford Cancer Center

Palo Alto, United States, 94304

Status
Completed
 
Locations

Sun Yat-sen University Cancer Center

Guangzhou, China, 510060

Status
Recruiting
 
Locations

Zhongshan Hospital, Fudan University

Shanghai, China, 200032

Status
Recruiting
 
Locations

Sichuan University West China Hospital

Chengdu, China

Status
Recruiting
 
Locations

Beijing Cancer Hospital

Beijing, China, 100142

Status
Recruiting
 
Locations

Charité Comprehensive Cancer Center (CCCC)

Berlin, Germany, 12203

Status
Recruiting
 
Locations

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08023

Status
Recruiting
 
Locations

Centro Integral Oncológico Clara Campal

Madrid, Spain, 28050

Status
Recruiting
 
Locations

Fundacion Jimenez Diaz (Clinica de la Concepcion)

Madrid, Spain, 28040

Status
Recruiting
 
Locations

IPO Porto

Porto, Portugal, 4200-072

Status
Recruiting
 
Locations

Samsung Medical Center

Seoul, South Korea, 06351

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
Recruiting
 
Locations

National Cancer Center Singapore

Singapore, Singapore, 169610

Status
Recruiting
 
Locations

Nagoya University Hospital

Nagoya, Japan, 466-8560

Status
Active, not recruiting
 
Locations

The Cancer Institute Hospital of JFCR

Koto-ku, Japan, 135-8550

Status
Active, not recruiting
 
Locations

Hokkaido University Hospital

Sapporo, Japan, 060-8648

Status
Completed
 
Locations

Hospital General Universitario de Valencia

Valencia, Spain, 46014

Status
Recruiting
 
Locations

Hospital Universitario "Marqués de Valdecilla"

Santander, Spain, 39008

Status
Recruiting
 
Locations

National Taiwan University Hospital

Taipei, Taiwan, China, 100

Status
Recruiting
 
Locations

Chang Gung Memorial Hospital Kaohsiung

Kaohsiung, Taiwan, China, 833

Status
Recruiting
 
Locations

Tri-Service General Hospital

Taipei, Taiwan, China

Status
Recruiting
 
Locations

Asan Medical Center

Seoul, South Korea, 05505

Status
Recruiting
 
Locations

Hospital del Mar

Barcelona, Spain, 08003

Status
Recruiting
 
Locations

Hospital General Universitario Gregorio Marañón | Oncología

Madrid, Spain, 28007

Status
Recruiting
 
Locations

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain, 08036

Status
Recruiting
 
Locations

IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)

Milano, Italy, 20141

Status
Recruiting
 
Locations

A.O.U. di Bologna Policlinico S.Orsola Malpighi

Bologna, Italy, 40138

Status
Recruiting
 
Locations

A.S.U. Friuli Centrale - A. Regionale Coordinamento Salute

Udine, Italy, 33100

Status
Recruiting
 
Locations

Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.

Milano, Italy, 20089

Status
Recruiting
 
Locations

Istituto Oncologico Veneto IRCCS (IOV)

Padova, Italy, 35128

Status
Recruiting
 
Locations

A.O.R.N. San Giuseppe Moscati

Avellino, Italy, 83100

Status
Recruiting
 
Locations

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy, 00168

Status
Recruiting
 
Locations

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Status
Recruiting
 
Locations

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Brazil, 90050-170

Status
Recruiting
 
Locations

Russian Oncological Scientific Center n.a. N.N. Blokhin RAMS

Moscow, Russia, 115478

Status
Recruiting
 
Locations

Moscow Scient. Res. Institute of Oncology n.a P.A. Hertzen

Moscow, Russia, 125284

Status
Recruiting
 
Locations

Ltd "EVIMED"

Chelyabinsk, Russia, 454048

Status
Recruiting
 
Locations

Arkhangelsk Clinical Oncology Dispensary

Arkhangelsk, Russia, 163045

Status
Recruiting
 
Locations

City Oncological Hospital #62

Moscow, Russia, 143423

Status
Recruiting
 
Locations

Clinical Diagnostical Center

Nizhny Novgorod, Russia, 603006

Status
Recruiting
 
Locations

1st Moscow State Medical University n.a. I.M.Sechenov

Moscow, Russia, 119435

Status
Recruiting
 
Locations

Korea University Anam Hospital

Seoul, South Korea, 136-705

Status
Recruiting
 
Locations

Narodny onkologicky ustav

Bratislava, Slovakia, 833 10

Status
Recruiting
 
Locations

Onkologicky Ustav Svatej Alzbety, s.r.o.

Bratislava, Slovakia, 812 50

Status
Recruiting
 
Locations

Hospital de Base da Fundação F M S J Rio Preto

São José do Rio Preto, Brazil, 15090-000

Status
Recruiting
 
Locations

Karolinska Universitetssjukhuset i Solna

Stockholm, Sweden, 171 76

Status
Recruiting
 
Locations

Wojskowy Instytut Medyczny

Warszawa, Poland, 04-141

Status
Recruiting
 
Locations

Fakultni Thomayerova Nemocnice

Praha 4, Czech Republic, 140 59

Status
Recruiting
 
Locations

Fakultni Nemocnice Olomouc

Olomouc, Czech Republic, 77900

Status
Recruiting
 
Locations

Masarykuv onkologicky ustav

Brno, Czech Republic, 65 653

Status
Recruiting
 
Locations

Fakultni Nemocnice Hradec Kralove

Hradec Kralove, Czech Republic, 500 05

Status
Recruiting
 
Locations

Orszagos Onkologiai Intezet

Budapest, Hungary, 1122

Status
Recruiting
 
Locations

Hôpital de la Milétrie

POITIERS cedex, France, 86021

Status
Recruiting
 
Locations

Centre Antoine Lacassagne

NICE CEDEX 2, France, 06102

Status
Recruiting
 
Locations

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom, G12 0YN

Status
Recruiting
 
Locations

Macquarie University Hospital

Macquarie University, Australia, 2109

Status
Recruiting
 
Locations

St John of God Healthcare

Subiaco, Australia, 6008

Status
Recruiting
 
Locations

Royal Darwin Hospital

Tiwi, Australia, 0810

Status
Recruiting
 
Locations

Hopital Saint Antoine - Paris

PARIS, France, 75012

Status
Recruiting
 
Locations

Hôpital de la Pitié-Salpétrière

PARIS, France, 75651

Status
Recruiting
 
Locations

Centre Hospitalier Lyon Sud

PIERRE BENITE, France, 69495

Status
Recruiting
 
Locations

ASST Grande Ospedale Metropolitano Niguarda

Milano, Italy, 20162

Status
Recruiting
 
Locations

IRCCS Ospedale Policlinico San Martino

Genova, Italy, 16132

Status
Recruiting
 
Locations

Hôpital Guillaume et René Laennec - Nantes

Saint Herblain, France, 44093

Status
Recruiting
 
Locations

Hopital Jean Minjoz

BESANCON, France, 25030

Status
Recruiting
 
Locations

Trakya Univ. Tip Fak.

Edirne, Turkey, 22030

Status
Recruiting
 
Locations

Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi

Istanbul, Turkey, 34098

Status
Recruiting
 
Locations

Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma

Izmir, Turkey, 35360

Status
Recruiting
 
Locations

Ankara Sehir Hastanesi

Ankara, Turkey, 06800

Status
Recruiting
 
Locations

Erciyes Universitesi Tip Fakultesi

Kayseri, Turkey, 38039

Status
Recruiting
 
Locations

Istanbul Universitesi Istanbul Tip Fakultesi

Istanbul, Turkey, 34093

Status
Recruiting
 
Locations

Institut de Cancérologie de l'Ouest - Saint Herblain

Saint-Herblain, France, 44800

Status
Recruiting
 
Locations

Hôpital Saint Louis

PARIS, France, 75010

Status
Recruiting
 
Locations

ICANS - Institut de Cancérologie de Strasbourg Europe

STRASBOURG, France, 67033

Status
Recruiting
 
Locations

Associação Hospital de Caridade de Ijuí

Ijuí, Brazil, 98700-000

Status
Recruiting
 
Locations

IBCC - Instituto Brasileiro de Controle do Cancer

São Paulo, Brazil, 04014-002

Status
Recruiting
 
Locations

Hosp. Araujo Jorge da Associação de Combate ao Câncer

Goiânia, Brazil, 74605-070

Status
Recruiting
 
Locations

Clín. de Pesq. e Centro de Estudos em Onco Gineco Mamária

São Paulo, Brazil, 01317-000

Status
Recruiting
 
Locations

Cenantron Centro Avançado de Tratamento Oncológico, Ltda.

Belo Horizonte, Brazil, 30110-090

Status
Recruiting
 
Locations

INCA - Hospital do Cancer III

Rio de Janeiro, Brazil, 20560-121

Status
Recruiting
 
Locations

Fundação Pio XII – Hospital de Câncer de Barretos

Barretos, Brazil, 14784-400

Status
Recruiting
 
Locations

Instituto do Câncer do Estado de São Paulo

São Paulo, Brazil, 01246-000

Status
Recruiting
 
Locations

Hospital Sirio Libanes

Sao Paulo, Brazil, 01308-050

Status
Recruiting
 
Locations

Instituto Nacional do Câncer - INCA - HC II

Rio de Janeiro, Brazil, 20220-410

Status
Recruiting
 
Locations

Oncoclínicas Rio de Janeiro S.A

Rio de Janeiro, Brazil, 22250-905

Status
Recruiting
 
Locations

Real e Benemérita Associação Portuguesa de Beneficência

São Paulo, Brazil, 01323-001

Status
Recruiting
 
Locations

TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has

ISTANBUL, Turkey, 34724

Status
Recruiting
 
Locations

Instituto Nacional de Cancerología INC Colombia

Bogotá, Colombia, 111511

Status
Recruiting
 
Locations

Fundación Oftalmológica de Santander Carlos Ardila Lule

Floridablanca, Colombia, 681004

Status
Recruiting
 
Locations

Oncomédica S.A.

Montería, Colombia, 230002

Status
Recruiting
 
Locations

Radium Hospital Department of Oncology

Oslo, Norway, 0379

Status
Recruiting
 
Locations

Instituto de Oncología de Rosario

Rosario, Argentina, S2000KZE

Status
Recruiting
 
Locations

Hospital Alemán

Buenos Aires, Argentina

Status
Recruiting
 
Locations

MH Egeszsegugyi Kozpont

Budapest, Hungary, 1062

Status
Recruiting
 
Locations

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

Status
Recruiting
 
Locations

Bacs-Kiskun Megyei Korhaz

Kecskemet, Hungary, 6000

Status
Recruiting
 
Locations

Hôpital Saint André - Bordeaux

BORDEAUX, France, 33000

Status
Recruiting
 
Locations

St. Petersburg Clinical Onc. Cent. of Spec. Types of Care

St. Petersburg, Russia, 197758

Status
Recruiting
 
Locations

Republican Clinical Oncology Dispensary Kazan

Kazan, Russia, 420029

Status
Recruiting
 
Locations

Fundacao Champalimaud

Lisboa, Portugal, 1400-038

Status
Recruiting
 
Locations

CHULN - Hospital Santa Maria

Lisboa, Portugal, 1649-035

Status
Recruiting
 
Locations

General Oncology Hospital of Kifissia AGIOI ANARGYROI

Kifissia / Athens, Greece, 14564

Status
Recruiting
 
Locations

LAIKO General Hospital of Athens

Athens, Greece, 11526

Status
Recruiting
 
Locations

AGIOS SAVVAS Anticancer Hospital of Athens

Athens, Greece, 115 22

Status
Recruiting
 
Locations

General Hospital of Athens "ALEXANDRA"

Athens, Greece, 11528

Status
Recruiting
 
Locations

University General Hospital of Patra

Patra, Greece, 26504

Status
Recruiting
 
Locations

London Regional Cancer Program, London Health Sciences Ctr

London, Canada, N6A 5W9

Status
Recruiting
 
Locations

Tom Baker Cancer Centre

Calgary, Canada, T2N 4N2

Status
Recruiting
 
Locations

Juravinski Cancer Centre-McMaster Medical Unit

Hamilton, Canada, L8V 5C2

Status
Recruiting
 
Locations

Institut Català d'Oncologia Hospitalet

Hospitalet de Llobregat, Spain, 08907

Status
Recruiting
 
Locations

Tata Memorial Hospital

Mumbai,, India, 400012

Status
Recruiting
 
Locations

Kokilaben Dhirubhai Ambani Hospital & Medical Research Insti

Mumbai, India, 400053

Status
Recruiting
 
Locations

All India Institute of Medical Sciences

New Delhi, India, 110029

Status
Recruiting
 
Locations

Jawaharlal Institute Of Postgraduate Medical Education and R

Gorimedu, India, 605006

Status
Recruiting
 
Locations

IRCCS Istituti Fisioterapici Ospitalieri - IFO

Roma, Italy, 00144

Status
Recruiting
 
Locations

Centre Léon Bérard

LYON CEDEX, France, 39373

Status
Recruiting
 
Locations

Uniklinik Heidelberg / NCT

Heidelberg, Germany, 69120

Status
Not yet recruiting
 
Locations

HCG Manavata Cancer Centre

Nashik, India, 422002

Status
Recruiting
 
Locations

Chittaranjan National Cancer Institute

Kolkata, India, 700026

Status
Recruiting
 

Trial Design