Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT02576431
Other study ID # 20289
Secondary ID LOXO-TRK-1500220
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date September 30, 2015
Est. completion date October 31, 2025

Study information

Verified date June 2024
Source Bayer
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 215
Est. completion date October 31, 2025
Est. primary completion date July 20, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms

  • Solid Tumors Harboring NTRK Fusion

Intervention

Drug:
BAY2757556 (Larotrectinib, Vitrakvi)
Larotrectinib will be administered orally as capsule or liquid solution at a dose of 100 mg twice daily in continuing 28-days cycles.

Locations

Country Name City State
Argentina Hospital Alemán Buenos Aires Ciudad Auton. De Buenos Aires
Brazil Fundacao Pio XII Hospital de Cancer de Barretos Barretos/SP Sao Paulo
Brazil IBCC - Instituto Brasileiro de Controle do Cancer São Paulo Sao Paulo
China Beijing Cancer Hospital Beijing
China Sichuan University West China Hospital Chengdu Sichuan
China Sun Yat-sen University Cancer Center Guangzhou Guangdong
China Zhongshan Hospital, Fudan University Shanghai
Czechia Fakultni Nemocnice Olomouc Olomouc
Denmark Finsen Centre Copenhagen
France Institut Bergonié - Unicancer Nouvelle Aquitaine Bordeaux Cedex
France Centre Antoine Lacassagne Nice Cedex 2
France Hôpital de la Pitié-Salpétrière Paris
France Hopital Saint Antoine - Paris Paris
France Institut de Cancérologie de l'Ouest - Saint Herblain Saint-Herblain
France ICANS - Institut de Cancérologie de Strasbourg Europe Strasbourg
Germany Charité Comprehensive Cancer Center (CCCC) Berlin
India All India Institute of Medical Sciences Bhubaneswar Delhi
India Jawaharlal Institute Of Postgraduate Medical Education and R Gorimedu Pondicherry
Ireland St Vincents University Hospital Dublin 4
Japan National Cancer Center Hospital East Kashiwa Chiba
Japan The Cancer Institute Hospital of JFCR Koto-ku Tokyo
Japan Nagoya University Hospital Nagoya Aichi
Japan Hokkaido University Hospital Sapporo Hokkaido
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Portugal IPO Porto Porto
Singapore National Cancer Center Singapore Singapore
Spain Ciutat Sanitaria i Universitaria de la Vall d'Hebron Barcelona
Spain Institut Català d'Oncologia Hospitalet Hospitalet de Llobregat Barcelona
Spain Centro Integral Oncológico Clara Campal Madrid
Spain Fundacion Jimenez Diaz (Clinica de la Concepcion) Madrid
Spain Hospital General Universitario Gregorio Maranon | Oncologia Madrid
Sweden Karolinska Universitetssjukhuset i Solna Stockholm
Taiwan Tri-Service General Hospital Taipei City
Turkey Health Ministry Of Türkiye Republic Ankara Bilkent City Hospital Ankara
Turkey Trakya Univ. Tip Fak. Edirne
Turkey Istanbul Universitesi Cerrahpasa-Cerrahpasa Tip Fakultesi Istanbul
Turkey TC Saglik Bakanligi Goztepe ProfDr Suleyman Yalcin Sehir Has Istanbul
Turkey Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Izmir
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States University of North Carolina Hospitals Chapel Hill North Carolina
United States University of Chicago Chicago Illinois
United States Cleveland Clinic Foundation Cleveland Ohio
United States Inova Schar Cancer Institute Fairfax Virginia
United States University of Texas MD Anderson Cancer Center Houston Texas
United States West Virginia University Morgantown West Virginia
United States Vanderbilt University Medical Center Nashville Tennessee
United States Memorial Sloan-Kettering Cancer Center New York New York
United States Stanford Cancer Center Palo Alto California
United States Memorial Hospital West Pembroke Florida
United States Fox Chase Cancer Center Philadelphia Pennsylvania
United States Thomas Jefferson University Philadelphia Pennsylvania
United States UCLA-Santa Monica Medical Center Santa Monica California
United States University of Washington Seattle Washington
United States Avera Cancer Institute Sioux Falls South Dakota
United States Wake Forest Baptist Health Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  China,  Czechia,  Denmark,  France,  Germany,  India,  Ireland,  Japan,  Korea, Republic of,  Portugal,  Singapore,  Spain,  Sweden,  Taiwan,  Turkey, 

References & Publications (1)

Waguespack SG, Drilon A, Lin JJ, Brose MS, McDermott R, Almubarak M, Bauman J, Casanova M, Krishnamurthy A, Kummar S, Leyvraz S, Oh DY, Park K, Sohal D, Sherman E, Norenberg R, Silvertown JD, Brega N, Hong DS, Cabanillas ME. Efficacy and safety of larotrectinib in patients with TRK fusion-positive thyroid carcinoma. Eur J Endocrinol. 2022 Apr 29;186(6):631-643. doi: 10.1530/EJE-21-1259. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Best overall response of confirmed complete response (CR) or partial response (PR) as determined by an independent radiology review committee using RECIST v1.1 or RANO criteria, as appropriate to tumor type. Up to 120 months
Secondary Best overall response of confirmed CR or PR as determined by the treating Investigator using RECIST v1.1 or RANO criteria, as appropriate to tumor type Up to 120 months
Secondary Duration of response (DOR): determined for subjects with best overall response of confirmed CR or PR by 1) an independent radiology review committee and 2) the treating Investigator Duration of response is the number of months from the start of confirmed complete response or partial response to disease progression or death. Complete response, partial response and disease progression are assessed by an independent radiology committee (IRC). Up to 120 months
Secondary Clinical benefit rate (CBR): best overall response of confirmed CR, PR, or stable disease lasting 16 or more weeks following the initiation of Larotrectinib Up to 120 months
Secondary Rate of subjects that have any tumor regression as a best response, measured as shrinkage of target lesions Up to 120 months
Secondary PFS: Number of months from initiation of larotrectinib to the earlier of disease progression or death due to any cause Up to 120 months
Secondary Overall Survival (OS): Number of months from the initiation of larotrectinib to the date of death due to any cause. Up to 120 months
Secondary Comparison of PFS following initiation of larotrectinib to that following the line of therapy immediately preceding larotrectinib in each subject who has received prior therapy Up to 120 months
Secondary Number of subjects with AEs categorized by severity. (including all, serious, and those considered treatment related.) Up to 120 months
Secondary Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration Up to 120 months
Secondary Severity of safety-relevant changes in clinical parameters or vital signs after drug administration Up to 120 months
Secondary Concordance coefficient Concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor with the diagnostic test being evaluated by the Sponsor. Up to 120 months
See also
  Status Clinical Trial Phase
Completed NCT02122913 - A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer Phase 1
Completed NCT03215511 - A Study to Test the Safety of the Investigational Drug Selitrectinib in Children and Adults That May Treat Cancer Phase 1
Completed NCT04275960 - Study in Healthy Adult Male Participants to Gather Information How the Human Body Absorbs, Distributes and Excretes the Study Drug Selitrectinib Including the Effect of the Interaction of Food With the Study Drug on the Human Body Phase 1
Completed NCT04771390 - Study to Compare How the Body Absorbs, Distributes and Excretes the Drug Selitrectinib (BAY2731954) Given as Two Different Tablet Formulations or as Liquid Formulations Including the Effect of Food on the Absorption, Distribution or Excretion of the Different Formulations in Healthy Participants Phase 1
Completed NCT05192642 - A Study Called VICTORIA to Learn More About How Well Larotrectinib Works in Adults With TRK Fusion-positive Cancer by Comparing Larotrectinib Data From Clinical Studies With Data of Other Treatments From Actual Practice
Active, not recruiting NCT02637687 - A Study to Test the Safety and Efficacy of the Drug Larotrectinib for the Treatment of Tumors With NTRK-fusion in Children Phase 1/Phase 2
No longer available NCT03206931 - Expanded Access to Provide Selitrectinib for the Treatment of Cancers With a NTRK Gene Fusion