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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02576431
Ethics application status
Date submitted
12/10/2015
Date registered
15/10/2015
Date last updated
19/11/2020

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 Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors
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

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

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_Lung cancer - Patients with lung cancer harboring NTRK fusions

Experimental: Arm 11_Melanoma - Patients with melanoma harboring NTRK fusions

Experimental: Arm 12_Breast cancer - Patient with non-secretory breast cancer harboring NTRK fusions


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 rate by IRC - Proportion of subjects with either complete response or partial response as determined by an independent radiology committee (IRC) using RECIST or RANO criteria.
Timepoint [1] 0 0
Up to 120 months
Secondary outcome [1] 0 0
Best overall response rate by investigator - Proportion of subjects with either complete response or partial response as determined by the treating investigator using RECIST or RANO criteria.
Timepoint [1] 0 0
Up to 120 months
Secondary outcome [2] 0 0
Duration of response (DOR) by IRC - 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).
Timepoint [2] 0 0
Up to 120 months
Secondary outcome [3] 0 0
Duration of response (DOR) by 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 the treating investigator.
Timepoint [3] 0 0
Up to 120 months
Secondary outcome [4] 0 0
Clinical benefit rate (CBR) - Proportion of subjects with best overall response of complete response, partial response or stable disease lasting 16 or more weeks following the initiation of larotrectinib.
Timepoint [4] 0 0
Up to 120 months
Secondary outcome [5] 0 0
Progression-free survival (PFS) after Larotrectinib - Number of months from initiation of larotrectinib to either disease progression or death due to any cause.
Timepoint [5] 0 0
Up to 120 months
Secondary outcome [6] 0 0
Overall survival time - 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
Progression-free survival (PFS) after past cancer therapy - Number of months from initiation of the line of therapy preceding larotrectinib to either disease progression or death due to any cause.
Timepoint [7] 0 0
Up to 120 months
Secondary outcome [8] 0 0
Number of subjects with adverse events
Timepoint [8] 0 0
Up to 120 months
Secondary outcome [9] 0 0
Number of subjects with serious adverse events
Timepoint [9] 0 0
Up to 120 months
Secondary outcome [10] 0 0
Number of subjects with treatment-related adverse events
Timepoint [10] 0 0
Up to 120 months
Secondary outcome [11] 0 0
Severity of adverse events
Timepoint [11] 0 0
Up to 120 months
Secondary outcome [12] 0 0
Severity of serious adverse events
Timepoint [12] 0 0
Up to 120 months
Secondary outcome [13] 0 0
Severity of treatment-related adverse events
Timepoint [13] 0 0
Up to 120 months
Secondary outcome [14] 0 0
Duration of adverse events
Timepoint [14] 0 0
Up to 120 months
Secondary outcome [15] 0 0
Duration of serious adverse events
Timepoint [15] 0 0
Up to 120 months
Secondary outcome [16] 0 0
Duration of treatment-related adverse events
Timepoint [16] 0 0
Up to 120 months
Secondary outcome [17] 0 0
Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration
Timepoint [17] 0 0
Up to 120 months
Secondary outcome [18] 0 0
Severity of safety-relevant changes in clinical parameters or vital signs after drug administration
Timepoint [18] 0 0
Up to 120 months
Secondary outcome [19] 0 0
Proportion of subjects that has any tumor regression as a best response
Timepoint [19] 0 0
Up to 120 months
Secondary outcome [20] 0 0
Concordance coefficient - Describes the concordance of prior molecular profiling that detected an NTRK fusion within the subject's tumor and a diagnostic test being evaluated by the sponsor
Timepoint [20] 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

- Subjects must have received prior standard therapy appropriate for their tumor type
and stage of disease, or 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
Minimum age
12 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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.

- Active uncontrolled systemic bacterial, viral, or fungal infection, unstable
cardiovascular disease, or other systemic disease that would limit compliance with
study procedures.

- Pregnancy or lactation.

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,NT,QLD,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [2] 0 0
Macquarie University Hospital - Sydney
Recruitment hospital [3] 0 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [4] 0 0
Royal Brisbane & Women's Hospital - Brisbane
Recruitment hospital [5] 0 0
St John of God Healthcare - Subiaco
Recruitment hospital [6] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
2109 - Sydney
Recruitment postcode(s) [3] 0 0
0810 - Tiwi
Recruitment postcode(s) [4] 0 0
4029 - Brisbane
Recruitment postcode(s) [5] 0 0
6008 - Subiaco
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment outside Australia
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California
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Glasgow
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London

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

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT02576431
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02576431