A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

Trial Title: A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

NCT ID: NCT02576431

Condition: Solid Tumors Harboring NTRK Fusion

Conditions: Keywords:
Non-small cell lung cancer
Thyroid cancer
Sarcoma
Colorectal cancer
Salivary gland cancer
Biliary cancer
Central nervous system (CNS) Tumor
Breast cancer
Melanoma
Neurotrophic tyrosine receptor kinase (NTRK)
NTRK1
NTRK2
NTRK3
Fusion Positive
TRK fusion
TRKA
TRKB
TRKC
ETV6

Study type: Interventional

Study phase: Phase 2

Overall status: Active, not recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: BAY2757556 (Larotrectinib, Vitrakvi)
Description: Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.
Arm group label: Arm 10_Prospective cohort
Arm group label: Arm 11_Bone health cohort
Arm group label: Arm 1_NSCLC
Arm group label: Arm 2_Thyroid
Arm group label: Arm 3_Sarcoma
Arm group label: Arm 4_Colorectal
Arm group label: Arm 5_Salivary
Arm group label: Arm 6_Biliary
Arm group label: Arm 7_Primary CNS
Arm group label: Arm 8_Other tumors
Arm group label: Arm 9_Solid tumors without confirmed NTRK fusion

Other name: LOXO-101

Summary: 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.

Detailed description: The primary objective of this study is to investigate the efficacy of larotrectinib for the treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor kinase (NTRK) of types 1-3 in children and adults. Secondary objectives comprise the efficacy and safety of larotrectinib in different NTRK-tumor types.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at CLIA or other similarly-certified laboratories. Subjects who have an NTRK gene fusion identified in a lab where CLIA or equivalent certification cannot be confirmed by the Sponsor at the time of consent may have been enrolled in Cohort 9 as per protocol versions 1.0 - 8.0. From protocol version 9.0: CLIA or similar certification of the lab performing the fusion assay is required. However, patients may be included after discussion with the sponsor if the lab performing the fusion assay is not CLIA or similar certified. - 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 (Eisenhauer et al. 2009). 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: 1. 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. 2. 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. 3. 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. 4. 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: 5. 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). 6. Subjects with primary CNS tumors must be neurologically stable based on stable neurologic exam for 7 days prior to enrollment. - At least 18 years of age - 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. - Adequate organ function as defined by the following criteria: 1. Serum AST and serum ALT < 2.5 x upper limit of normal (ULN), or AST and ALT < 5 x ULN if liver function abnormalities are due to underlying malignancy 2. Total bilirubin < 2.5 x ULN, except in the setting of biliary obstruction. Subjects with a known history of Gilberts Disease and an isolated elevation of indirect bilirubin are eligible 3. Serum creatinine < 2.0 x ULN OR an estimated glomerular filtration rate ≥ 30 mL/minute using the Cockcroft-Gault formula: (140- age) x body weight (kg) x 0.85 (if female)/serum creatinine (mg/dL) x 72 with either result acceptable for enrollment. - Ability to comply (or for guardian to ensure compliance) with outpatient treatment, laboratory monitoring, and required clinic visits for the duration of study participation. - 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: - Investigational agent or anticancer therapy within 2 weeks prior to the planned start of larotrectinib or 5 half-lives, whichever is shorter, and without recovery of acute and/or clinically significant toxicities from that therapy. - Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting 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 CNS tumors are eligible. - Uncontrolled concurrent malignancy that would limit assessment of efficacy of larotrectinib. Allowed conditions may include, but are not limited to in situ cancers of cervix, breast, or skin, superficial bladder cancer, limited-stage prostate cancer, and basal or squamous cancers of the skin. - Active uncontrolled systemic bacterial, viral, or fungal infection CTCAE grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures. Unstable cardiovascular disease is defined as: 1. In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy. 2. Myocardial infarction within 3 months of screening. 3. Stroke within 3 months of screening. - Inability to discontinue treatment with a strong CYP3A4 inhibitor or inducer - Currently recovering from AEs/ ADRs due to previous treatments (excluding alopecia). Inclusion is only advised once the AE/ADR resolves or recovers to baseline or at least to CTCAE grade 1. - Known or suspected hypersensitivity against the active substance or any of the ingredients of the IMP. - Known history of HIV infection. All patients must be screened for HIV up to 28 days prior to study drug start using a blood test for HIV according to local regulations. - HBV or HCV infection. All patients must be screened for HBV and HCV up to 28 days prior to study drug start using the routine hepatitis virus laboratorial panel. Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBVDNA. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Stanford Cancer Center

Address:
City: Palo Alto
Zip: 94304
Country: United States

Facility:
Name: UCLA-Santa Monica Medical Center

Address:
City: Santa Monica
Zip: 90404
Country: United States

Facility:
Name: Memorial Hospital West

Address:
City: Pembroke
Zip: 33028
Country: United States

Facility:
Name: The University of Chicago Medical Center (UCMC)

Address:
City: Chicago
Zip: 60637
Country: United States

Facility:
Name: Massachusetts General Hospital

Address:
City: Boston
Zip: 02114-2696
Country: United States

Facility:
Name: Dana-Farber Cancer Institute

Address:
City: Boston
Zip: 2215
Country: United States

Facility:
Name: Memorial Sloan-Kettering Cancer Center

Address:
City: New York
Zip: 10065
Country: United States

Facility:
Name: University of North Carolina Hospitals

Address:
City: Chapel Hill
Zip: 27312
Country: United States

Facility:
Name: Wake Forest Baptist Health

Address:
City: Winston-Salem
Zip: 27157
Country: United States

Facility:
Name: Cleveland Clinic Foundation

Address:
City: Cleveland
Zip: 44195
Country: United States

Facility:
Name: Thomas Jefferson University

Address:
City: Philadelphia
Zip: 19107
Country: United States

Facility:
Name: Fox Chase Cancer Center

Address:
City: Philadelphia
Zip: 19111-2497
Country: United States

Facility:
Name: Avera Cancer Institute

Address:
City: Sioux Falls
Zip: 57105
Country: United States

Facility:
Name: Vanderbilt University Medical Center

Address:
City: Nashville
Zip: 37232
Country: United States

Facility:
Name: University of Texas MD Anderson Cancer Center

Address:
City: Houston
Zip: 77030
Country: United States

Facility:
Name: Inova Schar Cancer Institute

Address:
City: Fairfax
Zip: 22031
Country: United States

Facility:
Name: University of Washington

Address:
City: Seattle
Zip: 98195
Country: United States

Facility:
Name: West Virginia University

Address:
City: Morgantown
Zip: 26505
Country: United States

Facility:
Name: Centro Estudios Médicos e Invest. Clínicas "Dr. N. Quirno"

Address:
City: Buenos Aires
Zip: TBC
Country: Argentina

Facility:
Name: Hospital Alemán

Address:
City: Buenos Aires
Zip: TBC
Country: Argentina

Facility:
Name: Fundación Cenit para la Investigación en Neurociencias

Address:
City: Caba
Zip: C1125 ABD
Country: Argentina

Facility:
Name: Centro Medico Austral

Address:
City: TBC
Zip: C1019ABS
Country: Argentina

Facility:
Name: Centro Médico San Roque

Address:
City: San Miguel de Tucumán
Zip: T4000HXU
Country: Argentina

Facility:
Name: Macquarie University Hospital

Address:
City: Sydney
Zip: 2109
Country: Australia

Facility:
Name: Royal Darwin Hospital

Address:
City: Tiwi
Zip: 810
Country: Australia

Facility:
Name: St John of God Healthcare

Address:
City: Subiaco
Zip: 6008
Country: Australia

Facility:
Name: Institut Jules Bordet/Jules Bordet Instituut

Address:
City: Bruxelles
Zip: 1070
Country: Belgium

Facility:
Name: Hosp. Araujo Jorge da Associação de Combate ao Câncer

Address:
City: Goiânia
Zip: 74605-070
Country: Brazil

Facility:
Name: Cenantron Centro Avançado de Tratamento Oncológico, Ltda.

Address:
City: Belo Horizonte
Zip: 30130-090
Country: Brazil

Facility:
Name: Fundacao Pio XII - Hospital de Cancer de Barretos

Address:
City: Barretos/SP
Zip: 14784-400
Country: Brazil

Facility:
Name: Instituto do Cancer do Estado de Sao Paulo

Address:
City: São Paulo
Zip: 01246-000
Country: Brazil

Facility:
Name: Real e Benemérita Associação Portuguesa de Beneficência

Address:
City: São Paulo
Zip: 01323-001
Country: Brazil

Facility:
Name: IBCC - Instituto Brasileiro de Controle do Cancer

Address:
City: São Paulo
Zip: 03102-002
Country: Brazil

Facility:
Name: Instituto Nacional do Câncer - INCA - HC II

Address:
City: Rio de Janeiro
Zip: 20081-250
Country: Brazil

Facility:
Name: INCA - Hospital do Cancer III

Address:
City: Rio de Janeiro
Zip: 20560-120
Country: Brazil

Facility:
Name: Oncoclínicas Rio de Janeiro S.A

Address:
City: Rio de Janeiro
Zip: 22250-905
Country: Brazil

Facility:
Name: Hospital Sirio Libanes

Address:
City: Sao Paulo
Zip: 01409-000
Country: Brazil

Facility:
Name: Tom Baker Cancer Centre

Address:
City: Calgary
Zip: T2N 4N2
Country: Canada

Facility:
Name: Sun Yat-sen University Cancer Center

Address:
City: Guangzhou
Zip: 510000
Country: China

Facility:
Name: Sichuan University West China Hospital

Address:
City: Chengdu
Zip: MISSING
Country: China

Facility:
Name: Beijing Cancer Hospital

Address:
City: Beijing
Zip: 100142
Country: China

Facility:
Name: Zhongshan Hospital, Fudan University

Address:
City: Shanghai
Zip: 200032
Country: China

Facility:
Name: Instituto Nacional de Cancerología INC Colombia

Address:
City: Bogota
Zip: 111511
Country: Colombia

Facility:
Name: Oncomédica S.A.

Address:
City: Montería
Zip: 230002
Country: Colombia

Facility:
Name: Fundación Oftalmológica de Santander Carlos Ardila Lule

Address:
City: Florida Blanca
Zip: 681004
Country: Colombia

Facility:
Name: Fakultní Nemocnice Olomouc

Address:
City: Olomouc
Zip: 77900
Country: Czechia

Facility:
Name: Rigshospitalet - Kræftbehandling

Address:
City: Copenhagen OE
Zip: 2100
Country: Denmark

Facility:
Name: Hopital Jean Minjoz

Address:
City: Besancon
Zip: 25030
Country: France

Facility:
Name: Institut Bergonié - Unicancer Nouvelle Aquitaine

Address:
City: Bordeaux Cedex
Zip: 33076
Country: France

Facility:
Name: Hopital Saint Antoine - Paris

Address:
City: Clamart
Zip: 92141
Country: France

Facility:
Name: Centre Antoine Lacassagne

Address:
City: Nice Cedex 2
Zip: 6189
Country: France

Facility:
Name: Hôpital de la Pitié-Salpétrière

Address:
City: Paris
Zip: 75651
Country: France

Facility:
Name: Hôpital de la Milétrie

Address:
City: Poitiers
Zip: 86021
Country: France

Facility:
Name: Institut de Cancérologie de l'Ouest - Saint Herblain

Address:
City: Saint-Herblain
Zip: 44800
Country: France

Facility:
Name: ICANS - Institut de Cancérologie de Strasbourg Europe

Address:
City: Strasbourg
Zip: 67033
Country: France

Facility:
Name: Charité Comprehensive Cancer Center (CCCC)

Address:
City: Berlin
Zip: 12203
Country: Germany

Facility:
Name: All India Institute of Medical Sciences

Address:
City: Bhubaneswar
Zip: 751019
Country: India

Facility:
Name: Jawaharlal Institute Of Postgraduate Medical Education and R

Address:
City: Gorimedu
Zip: 605006
Country: India

Facility:
Name: St Vincents University Hospital

Address:
City: Dublin 4
Zip: TBC
Country: Ireland

Facility:
Name: A.O.R.N. San Giuseppe Moscati

Address:
City: Avellino
Zip: 83100
Country: Italy

Facility:
Name: A.O.U. di Bologna Policlinico S.Orsola Malpighi

Address:
City: Bologna
Zip: 40138
Country: Italy

Facility:
Name: A.S.U. Friuli Centrale - A. Regionale Coordinamento Salute

Address:
City: Udine
Zip: 33038
Country: Italy

Facility:
Name: IRCCS Istituti Fisioterapici Ospitalieri - IFO

Address:
City: Roma
Zip: 144
Country: Italy

Facility:
Name: Istituto Europeo di Oncologia s.r.l

Address:
City: Milano
Zip: 20141
Country: Italy

Facility:
Name: Istituto Oncologico Veneto

Address:
City: Padova
Zip: 35128
Country: Italy

Facility:
Name: Nagoya University Hospital

Address:
City: Nagoya
Zip: 466-8560
Country: Japan

Facility:
Name: National Cancer Center Hospital East

Address:
City: Kashiwa
Zip: 277-8577
Country: Japan

Facility:
Name: Hokkaido University Hospital

Address:
City: Sapporo
Zip: 060-8648
Country: Japan

Facility:
Name: The Cancer Institute Hospital of JFCR

Address:
City: Koto-ku
Zip: 135-8550
Country: Japan

Facility:
Name: Seoul National University Hospital

Address:
City: Seoul
Zip: 3080
Country: Korea, Republic of

Facility:
Name: Severance Hospital, Yonsei University Health System

Address:
City: Seoul
Zip: 03722
Country: Korea, Republic of

Facility:
Name: Asan Medical Center

Address:
City: Seoul
Zip: 138-736
Country: Korea, Republic of

Facility:
Name: Samsung Medical Center

Address:
City: Seoul
Zip: 6351
Country: Korea, Republic of

Facility:
Name: IPO Porto

Address:
City: Porto
Zip: 4200-072
Country: Portugal

Facility:
Name: Arkhangelsk Clinical Oncology Dispensary

Address:
City: Arkhangelsk
Zip: 163045
Country: Russian Federation

Facility:
Name: Republican Clinical Oncology Dispensary Kazan

Address:
City: Kazan
Zip: 420029
Country: Russian Federation

Facility:
Name: Russian Oncological Scientific Center n.a. N.N. Blokhin RAMS

Address:
City: Moscow
Zip: 115478
Country: Russian Federation

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

Address:
City: Moscow
Zip: 119991
Country: Russian Federation

Facility:
Name: Clinical Diagnostical Center

Address:
City: Nizhny Novgorod
Zip: 603006
Country: Russian Federation

Facility:
Name: St. Petersburg Clinical Onc. Cent. of Spec. Types of Care

Address:
City: St. Petersburg
Zip: 197758
Country: Russian Federation

Facility:
Name: National Cancer Center Singapore

Address:
City: Singapore
Zip: 168583
Country: Singapore

Facility:
Name: Onkologicky Ustav Svatej Alzbety, s.r.o.

Address:
City: Bratislava
Zip: 812 50
Country: Slovakia

Facility:
Name: Narodny onkologicky ustav

Address:
City: Bratislava
Zip: 833 10
Country: Slovakia

Facility:
Name: Institut Català d'Oncologia Hospitalet

Address:
City: Hospitalet de Llobregat
Zip: 08907
Country: Spain

Facility:
Name: Hospital del Mar

Address:
City: Barcelona
Zip: 08003
Country: Spain

Facility:
Name: Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Address:
City: Barcelona
Zip: 08035
Country: Spain

Facility:
Name: Hospital General Universitario Gregorio Maranon | Oncologia

Address:
City: Madrid
Zip: 28007
Country: Spain

Facility:
Name: Fundacion Jimenez Diaz (Clinica de la Concepcion)

Address:
City: Madrid
Zip: 28040
Country: Spain

Facility:
Name: Centro Integral Oncológico Clara Campal

Address:
City: Madrid
Zip: 28050
Country: Spain

Facility:
Name: Karolinska Universitetssjukhuset i Solna

Address:
City: Stockholm
Zip: 171 76
Country: Sweden

Facility:
Name: Tri-Service General Hospital

Address:
City: Taipei City
Zip: 114
Country: Taiwan

Facility:
Name: Health Ministry Of Türkiye Republic Ankara Bilkent City Hospital

Address:
City: Ankara
Zip: 6800
Country: Turkey

Facility:
Name: Trakya Univ. Tip Fak.

Address:
City: Edirne
Zip: 22030
Country: Turkey

Facility:
Name: Istanbul Universitesi Istanbul Tip Fakultesi

Address:
City: Istanbul
Zip: 34093
Country: Turkey

Facility:
Name: Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi

Address:
City: Istanbul
Zip: 34098
Country: Turkey

Facility:
Name: TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has

Address:
City: Istanbul
Zip: 34722
Country: Turkey

Facility:
Name: Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma

Address:
City: Izmir
Zip: 35360
Country: Turkey

Facility:
Name: Erciyes Universitesi Tip Fakultesi

Address:
City: Kayseri
Zip: 38039
Country: Turkey

Start date: September 30, 2015

Completion date: October 31, 2025

Lead sponsor:
Agency: Bayer
Agency class: Industry

Source: Bayer

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT02576431
https://clinicaltrials.bayer.com/