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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02576431




Registration number
NCT02576431
Ethics application status
Date submitted
12/10/2015
Date registered
15/10/2015

Titles & IDs
Public title
A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors
Scientific title
A Study to Learn How Well the Drug Larotrectinib Works in Adults With Different Solid Cancers With a Change in the Genes Called NTRK Fusion
Secondary ID [1] 0 0
LOXO-TRK-15002
Secondary ID [2] 0 0
20289
Universal Trial Number (UTN)
Trial acronym
NAVIGATE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumors Harboring NTRK Fusion 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - BAY2757556 (Larotrectinib, Vitrakvi)

Experimental: Arm 1_NSCLC - Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)

Experimental: Arm 2_Thyroid - Patients with solid thyroid tumors harboring NTRK fusions (arm closed)

Experimental: Arm 3_Sarcoma - Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)

Experimental: Arm 4_Colorectal - Patients with solid colorectal tumors harboring NTRK fusions (arm closed)

Experimental: Arm 5_Salivary - Patients with solid salivary tumors harboring NTRK fusions (arm closed)

Experimental: Arm 6_Biliary - Patients with solid biliary tumors harboring NTRK fusions (arm closed)

Experimental: Arm 7_Primary CNS - Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)

Experimental: Arm 8_Other tumors - Patients with e.g. kidney cancer, squamous cell cancer of head or neck or ovarian solid tumors harboring NTRK fusions (arm closed)

Experimental: Arm 9_Solid tumors without confirmed NTRK fusion - Patients eligible for arms 1 to 8, but with documented NTRK fusion from a laboratory where CLIA or equivalent certification cannot be confirmed by the sponsor at the time of consent (arm closed)

Experimental: Arm 10_Prospective cohort - Patients with melanoma, non secretory breast and colorectal cancer or other tumor types harboring NTRK fusions, except soft tissue sarcoma, salivary gland and thyroid cancer (arm closed)

Experimental: Arm 11_Bone health cohort - Patients with all tumor types harboring NTRK fusions, not eligible for the main prospective cohort, including patients with non-measurable disease


Treatment: Drugs: 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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 120 months
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Up to 120 months
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 120 months
Secondary outcome [3] 0 0
Clinical benefit rate (CBR): best overall response of confirmed CR, PR, or stable disease lasting 16 or more weeks following the initiation of Larotrectinib
Timepoint [3] 0 0
Up to 120 months
Secondary outcome [4] 0 0
Rate of subjects that have any tumor regression as a best response, measured as shrinkage of target lesions
Timepoint [4] 0 0
Up to 120 months
Secondary outcome [5] 0 0
PFS: Number of months from initiation of larotrectinib to the earlier of disease progression or death due to any cause
Timepoint [5] 0 0
Up to 120 months
Secondary outcome [6] 0 0
Overall Survival (OS): Number of months from the initiation of larotrectinib to the date of death due to any cause.
Timepoint [6] 0 0
Up to 120 months
Secondary outcome [7] 0 0
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
Timepoint [7] 0 0
Up to 120 months
Secondary outcome [8] 0 0
Number of subjects with AEs categorized by severity. (including all, serious, and those considered treatment related.)
Timepoint [8] 0 0
Up to 120 months
Secondary outcome [9] 0 0
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Timepoint [9] 0 0
Up to 120 months
Secondary outcome [10] 0 0
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Timepoint [10] 0 0
Up to 120 months
Secondary outcome [11] 0 0
Concordance coefficient
Timepoint [11] 0 0
Up to 120 months

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/09/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/10/2025
Actual
Sample size
Target
Accrual to date
Final
215
Recruitment in Australia
Recruitment state(s)
NSW,NT,WA
Recruitment hospital [1] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [3] 0 0
St John of God Healthcare - Subiaco
Recruitment postcode(s) [1] 0 0
2109 - Sydney
Recruitment postcode(s) [2] 0 0
810 - Tiwi
Recruitment postcode(s) [3] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
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Illinois
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United States of America
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Massachusetts
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United States of America
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New York
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North Carolina
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Ohio
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United States of America
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Pennsylvania
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United States of America
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South Dakota
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Virginia
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United States of America
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Washington
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United States of America
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West Virginia
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Argentina
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Ciudad Auton. De Buenos Aires
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Argentina
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Tucuman
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Belgium
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Bruxelles
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Brazil
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Goiás
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Brazil
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Minas Gerais
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Brazil
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Sao Paulo
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Brazil
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Rio de Janeiro
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Canada
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Alberta
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China
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Guangdong
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China
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Sichuan
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China
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Beijing
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China
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Shanghai
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Colombia
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Colombia
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Córdoba
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Colombia
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Santander
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Czechia
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Olomouc
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Denmark
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Copenhagen OE
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France
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Besancon
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France
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Bordeaux Cedex
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France
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Clamart
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France
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Nice Cedex 2
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France
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Paris
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France
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Poitiers
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France
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Saint-Herblain
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France
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Strasbourg
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Germany
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Berlin
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India
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Odisha
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India
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Pondicherry
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Campania
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Italy
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Italy
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Italy
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Lazio
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Italy
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Lombardia
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Italy
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Veneto
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Aichi
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Chiba
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Hokkaido
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Japan
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Tokyo
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Korea, Republic of
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Seoul Teugbyeolsi
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Korea, Republic of
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Seoul
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Portugal
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Porto
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Russian Federation
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Arkhangelsk
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Russian Federation
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Kazan
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Russian Federation
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Moscow
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Russian Federation
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Nizhny Novgorod
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Russian Federation
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St. Petersburg
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Singapore
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Singapore
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Slovakia
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Bratislava
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Spain
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Barcelona
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Spain
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Madrid
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Sweden
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Stockholm
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Taiwan
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Taipei City
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Turkey
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Ankara
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Turkey
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Edirne
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Kayseri

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Bayer Clinical Trials Contact
Address 0 0
Country 0 0
Phone 0 0
(+)1-888-84 22937
Fax 0 0
Email 0 0
clinical-trials-contact@bayer.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT02576431