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

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ClinicalTrials.gov Identifier: NCT02576431
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : October 25, 2021
Sponsor:
Information provided by (Responsible Party):
Bayer

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.

Condition or disease Intervention/treatment Phase
Solid Tumors Harboring NTRK Fusion Drug: BAY2757556 (Larotrectinib, Vitrakvi) Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Basket Study of the Oral TRK Inhibitor Larotrectinib in Subjects With NTRK Fusion-positive Tumors
Actual Study Start Date : September 30, 2015
Estimated Primary Completion Date : August 15, 2023
Estimated Study Completion Date : September 30, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 1_NSCLC
Patients with solid non-small cell lung cancer (NSCLC) harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

Experimental: Arm 2_Thyroid
Patients with solid thyroid tumors harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

Experimental: Arm 3_Sarcoma
Patients with soft-tissue sarcoma harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

Experimental: Arm 4_Colorectal
Patients with solid colorectal tumors harboring NTRK fusions
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.
Other Name: LOXO-101

Experimental: Arm 5_Salivary
Patients with solid salivary tumors harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

Experimental: Arm 6_Biliary
Patients with solid biliary tumors harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

Experimental: Arm 7_Primary CNS
Patients with solid tumors in the primary central nervous system (CNS) harboring NTRK fusions (arm closed)
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.
Other Name: LOXO-101

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
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.
Other Name: LOXO-101

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)
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.
Other Name: LOXO-101

Experimental: Arm 10- Perspective cohort
Patients with melanoma, non secretory breast and colorectal cancer harboring NTRK fusions.
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.
Other Name: LOXO-101




Primary Outcome Measures :
  1. Best overall response rate by IRC [ Time Frame: Up to 120 months ]
    Proportion of subjects with either complete response or partial response as determined by an independent radiology committee (IRC) using RECIST or RANO criteria.


Secondary Outcome Measures :
  1. Best overall response rate by investigator [ Time Frame: Up to 120 months ]
    Proportion of subjects with either complete response or partial response as determined by the treating investigator using RECIST or RANO criteria.

  2. Duration of response (DOR) by IRC [ Time Frame: Up to 120 months ]
    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).

  3. Duration of response (DOR) by investigator [ Time Frame: Up to 120 months ]

    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.


  4. Clinical benefit rate (CBR) [ Time Frame: Up to 120 months ]
    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.

  5. Progression-free survival (PFS) after Larotrectinib [ Time Frame: Up to 120 months ]
    Number of months from initiation of larotrectinib to either disease progression or death due to any cause.

  6. Overall survival time [ Time Frame: Up to 120 months ]
    Number of months from the initiation of larotrectinib to the date of death due to any cause.

  7. Progression-free survival (PFS) after past cancer therapy [ Time Frame: Up to 120 months ]
    Number of months from initiation of the line of therapy preceding larotrectinib to either disease progression or death due to any cause.

  8. Number of subjects with adverse events [ Time Frame: Up to 120 months ]
  9. Number of subjects with serious adverse events [ Time Frame: Up to 120 months ]
  10. Number of subjects with treatment-related adverse events [ Time Frame: Up to 120 months ]
  11. Severity of adverse events [ Time Frame: Up to 120 months ]
  12. Severity of serious adverse events [ Time Frame: Up to 120 months ]
  13. Severity of treatment-related adverse events [ Time Frame: Up to 120 months ]
  14. Duration of adverse events [ Time Frame: Up to 120 months ]
  15. Duration of serious adverse events [ Time Frame: Up to 120 months ]
  16. Duration of treatment-related adverse events [ Time Frame: Up to 120 months ]
  17. Number of subjects with safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 120 months ]
  18. Severity of safety-relevant changes in clinical parameters or vital signs after drug administration [ Time Frame: Up to 120 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion, identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) or other similarly-certified laboratories.
  • 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. 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.
  • 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.
  • 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.

Exclusion Criteria:

  • Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (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 central nervous system (CNS) tumors are eligible.
  • Pregnancy or lactation.
  • Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576431


Contacts
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Contact: Bayer Clinical Trials Contact (+)1-888-84 22937 clinical-trials-contact@bayer.com

Locations
Show Show 158 study locations
Sponsors and Collaborators
Bayer
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02576431    
Other Study ID Numbers: 20289
LOXO-TRK-15002 ( Other Identifier: Loxo Oncology, Inc )
2015-003582-28 ( EudraCT Number )
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: October 25, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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.clinicalstudydatarequest.com 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 Study sponsors section of the portal.


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bayer:
Sarcoma
Non-small cell lung cancer
Thyroid cancer
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
Additional relevant MeSH terms:
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Neoplasms