Breast Cancer Clinical Trial
A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors
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.
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.
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:
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.
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.
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.
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:
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).
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:
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
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
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.
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:
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.
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.
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There are 157 Locations for this study
Palo Alto California, 94304, United States
Santa Monica California, 90404, United States
Pembroke Florida, 33028, United States
Chicago Illinois, 60637, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Lebanon New Hampshire, 03756, United States
New York New York, 10065, United States
Chapel Hill North Carolina, 27599, United States
Winston-Salem North Carolina, 27157, United States
Cleveland Ohio, 44195, United States
Philadelphia Pennsylvania, 19107, United States
Philadelphia Pennsylvania, 19111, United States
Sioux Falls South Dakota, 57105, United States
Nashville Tennessee, 37232, United States
Houston Texas, 77030, United States
Fairfax Virginia, 22031, United States
Seattle Washington, 98109, United States
Morgantown West Virginia, 26505, United States
Buenos Aires Ciudad Auton. De Buenos Aires, C1019, Argentina
Buenos Aires Ciudad Auton. De Buenos Aires, C1280, Argentina
Buenos Aires Ciudad Auton. De Buenos Aires, CP: C, Argentina
Buenos Aires Ciudad Auton. De Buenos Aires, , Argentina
Caba Ciudad Auton. De Buenos Aires, C1125, Argentina
Caba Ciudad Auton. De Buenos Aires, C1426, Argentina
Rosario Santa Fe, S2000, Argentina
San Miguel de Tucumán Tucuman, T4000, Argentina
Macquarie University New South Wales, 2109, Australia
Tiwi Northern Territory, 0810, Australia
Subiaco Western Australia, 6008, Australia
Nedlands , 6009, Australia
Anderlecht , 1070, Belgium
Goiânia Goiás, 74605, Brazil
Belo Horizonte Minas Gerais, 30110, Brazil
Ijuí Rio Grande Do Sul, 98700, Brazil
Porto Alegre Rio Grande Do Sul, 90020, Brazil
Barretos/SP Sao Paulo, 14784, Brazil
São José do Rio Preto Sao Paulo, 15090, Brazil
São Paulo/SP Sao Paulo, 04014, Brazil
São Paulo Sao Paulo, 01246, Brazil
São Paulo Sao Paulo, 01317, Brazil
São Paulo Sao Paulo, 01323, Brazil
Rio de Janeiro , 20220, Brazil
Rio de Janeiro , 20560, Brazil
Rio de Janeiro , 22250, Brazil
Sao Paulo , 01308, Brazil
Calgary Alberta, T2N 4, Canada
Hamilton Ontario, L8V 5, Canada
London Ontario, N6A 5, Canada
Montreal Quebec, H3T 1, Canada
Guangzhou Guangdong, 51006, China
Chengdu Sichuan, , China
Beijing , 10014, China
Shanghai , 20003, China
Bogota Cundinamarca, 11151, Colombia
Montería Córdoba, 23000, Colombia
Florida Blanca Santander, 68100, Colombia
Brno , 65 65, Czechia
Hradec Kralove , 500 0, Czechia
Olomouc , 77900, Czechia
Prague , 140 5, Czechia
Copenhagen , 2100, Denmark
Besancon , 25030, France
Bordeaux Cedex , 33076, France
Bordeaux , 33000, France
Lyon Cedex , 39373, France
Nice Cedex 2 , 06102, France
Paris , 75010, France
Paris , 75012, France
Paris , 75651, France
Pierre Benite , 69495, France
POITIERS cedex , 86021, France
Saint Herblain , 44093, France
Saint-Herblain , 44800, France
Strasbourg , 67033, France
Heidelberg Baden-Württemberg, 69120, Germany
Düsseldorf Nordrhein-Westfalen, 40225, Germany
Essen Nordrhein-Westfalen, 45122, Germany
Berlin , 12203, Germany
Athens , 115 2, Greece
Athens , 11526, Greece
Athens , 11528, Greece
Kifissia / Athens , 14564, Greece
Patra , 26504, Greece
Budapest , 1062, Hungary
Budapest , 1122, Hungary
Debrecen , 4032, Hungary
Kecskemet , 6000, Hungary
New Delhi Delhi, 11002, India
Mumbai, Maharashtra, 40001, India
Mumbai Maharashtra, 40005, India
Nashik Maharashtra, 42200, India
Gorimedu Pondicherry, 60500, India
Kolkata West Bengal, 70002, India
Dublin , DUBLI, Ireland
Avellino Campania, 83100, Italy
Bologna Emilia-Romagna, 40138, Italy
Udine Friuli-Venezia Giulia, 33100, Italy
Roma Lazio, 00144, Italy
Roma Lazio, 00168, Italy
Genova Liguria, 16132, Italy
Milano Lombardia, 20089, Italy
Milano Lombardia, 20141, Italy
Milano Lombardia, 20162, Italy
Padova Veneto, 35128, Italy
Nagoya Aichi, 466-8, Japan
Kashiwa Chiba, 277-8, Japan
Sapporo Hokkaido, 060-8, Japan
Koto-ku Tokyo, 135-8, Japan
Seoul , 03080, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 136-7, Korea, Republic of
Seoul , 3722, Korea, Republic of
Oslo , 0379, Norway
Warszawa , 04-14, Poland
Lisboa , 1400-, Portugal
Lisboa , 1649-, Portugal
Porto , 4099-, Portugal
Porto , 4200-, Portugal
Arkhangelsk , 16304, Russian Federation
Chelyabinsk , 45404, Russian Federation
Kazan , 42002, Russian Federation
Moscow , 11112, Russian Federation
Moscow , 11547, Russian Federation
Moscow , 11943, Russian Federation
Moscow , 12528, Russian Federation
Moscow , 14342, Russian Federation
Nizhny Novgorod , 60300, Russian Federation
St. Petersburg , 19775, Russian Federation
Singapore , 16858, Singapore
Bratislava , 812 5, Slovakia
Bratislava , 833 1, Slovakia
Hospitalet de Llobregat Barcelona, 08907, Spain
Santander Cantabria, 39008, Spain
Barcelona , 08003, Spain
Barcelona , 08023, Spain
Barcelona , 08036, Spain
Madrid , 28007, Spain
Madrid , 28040, Spain
Madrid , 28050, Spain
Valencia , 46010, Spain
Valencia , 46014, Spain
Stockholm , 171 7, Sweden
Kaohsiung , 833, Taiwan
Taipei City , 114, Taiwan
Taipei , 100, Taiwan
Ankara , 6800, Turkey
Edirne , 22030, Turkey
Istanbul , 34093, Turkey
Istanbul , 34098, Turkey
Istanbul , 34724, Turkey
Izmir , 35360, Turkey
Kayseri , 38039, Turkey
Kiev , 03022, Ukraine
Southampton Hampshire, SO16 , United Kingdom
Glasgow , G12 0, United Kingdom
London , EC1M , United Kingdom
London , W1T 7, United Kingdom
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